From a1f8ec7dcf033b4d81d842dc383ef511d0bb6305 Mon Sep 17 00:00:00 2001 From: Susheel Varma Date: Sun, 3 Sep 2023 00:49:51 +0000 Subject: [PATCH] Commit new papers --- data/covid/ack-preprints.csv | 38 +- data/covid/papers.csv | 65 +- data/papers.csv | 418 +-- data/papers.json | 6420 +++++++++++++++++----------------- 4 files changed, 3489 insertions(+), 3452 deletions(-) diff --git a/data/covid/ack-preprints.csv b/data/covid/ack-preprints.csv index e27e3783..f129fd1f 100644 --- a/data/covid/ack-preprints.csv +++ b/data/covid/ack-preprints.csv @@ -16,8 +16,8 @@ PPR691339,https://doi.org/10.21203/rs.3.rs-2832054/v1,Insights into the implemen PPR550732,https://doi.org/10.1101/2022.09.27.22280397,Vaccine effectiveness for preventing COVID-19 hospital admission during pregnancy: a population-based cohort study in England during the Alpha and Delta waves of the SARS-CoV-2 pandemic,"Bosworth ML, Schofield R, Ayoubkhani D, Charlton L, Nafilyan V, Khunti K, Zaccardi F, Gillies C, Akbari A, Knight M, Wood R, Hardelid P, Zuccolo L, Harrison C.",,No Journal Info,2022,2022-09-27,Y,,,,"

Objective

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

Design

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

Setting

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

Participants

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

Main outcome measures

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

Results

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

Conclusions

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

What is already known on this topic

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

What this study adds

Our study provides real-world evidence that COVID-19 vaccination reduces the risk of hospital admission by a similar amount for both women infected with SARS-CoV-2 during pregnancy and women who were not pregnant when infected, during the Alpha and Delta dominant periods in England.",,doi:https://doi.org/10.1101/2022.09.27.22280397; html:https://europepmc.org/article/PPR/PPR550732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR550732&type=FILE&fileName=EMS155049-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/27/2022.09.27.22280397.full.pdf PPR506156,https://doi.org/10.1101/2022.06.09.22276196,Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,"van der Klaauw AA, Horner EC, Pereyra-Gerber P, Agrawal U, Foster WS, Spencer S, Vergese B, Smith M, Henning E, Ramsay ID, Smith JA, Guillaume SM, Sharpe HJ, Hay IM, Thompson S, Innocentin S, Booth LH, Robertson C, McCowan C, Mulroney TE, O’Reilly MJ, Gurugama TP, Gurugama LP, Rust MA, Ferreira A, Ebrahimi S, Ceron-Gutierrez L, Scotucci J, Kronsteiner B, Dunachie SJ, Klenerman P, Park AJ, Rubino F, Stark H, Kingston N, Doffinger R, Linterman MA, Matheson NJ, Sheikh A, Farooqi IS, Thaventhiran JED, PITCH Consortium.",,No Journal Info,2022,2022-06-14,N,,,,"

ABSTRACT

Obesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to Covid-19 amongst 3.5 million people in Scotland. Vaccinated people with severe obesity (BMI>40 kg/m 2 ) were significantly more likely to experience hospitalization or death from Covid-19. Excess risk increased with time since vaccination. To investigate the underlying mechanisms, we conducted a prospective longitudinal study of the immune response in a clinical cohort of vaccinated people with severe obesity. Compared with normal weight people, six months after their second vaccine dose, significantly more people with severe obesity had unquantifiable titres of neutralizing antibody against authentic SARS-CoV-2 virus, reduced frequencies of antigen-experienced SARS-CoV-2 Spike-binding B cells, and a dissociation between anti-Spike antibody levels and neutralizing capacity. Neutralizing capacity was restored by a third dose of vaccine, but again declined more rapidly in people with severe obesity. We demonstrate that waning of SARS-CoV-2 vaccine-induced humoral immunity is accelerated in people with severe obesity and associated with increased hospitalization and mortality from breakthrough infections. Given the prevalence of obesity, our findings have significant implications for global public health.",,doi:https://doi.org/10.1101/2022.06.09.22276196; html:https://europepmc.org/article/PPR/PPR506156; doi:https://doi.org/10.1101/2022.06.09.22276196; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/14/2022.06.09.22276196.full.pdf PPR660616,https://doi.org/10.1101/2023.05.12.23289914,Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform,"The OpenSAFELY collaborative, Tazare J, Nab L, Zheng B, Hulme WJ, Green ACA, Curtis HJ, Mahalingasivam V, Higgins R, Schultze A, Bhaskaran K, Mehrkar A, Schaffer A, Smith RM, Bates C, Cockburn J, Parry J, Hester F, Harper S, Eggo RM, Walker AJ, Marks M, Brown M, Maringe C, Leyrat C, Evans SJW, Goldacre B, MacKenna B, Sterne JAC, Tomlinson LA, Douglas IJ.",,No Journal Info,2023,2023-05-16,Y,,,,"

Background

The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment.

Methods

With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk individuals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models.

Results

Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81;1.22) [BA.1] and 1.22 (0.96;1.56) [BA.2]; corresponding HRs for sotrovimab versus untreated were 0.76 (0.66;0.89) [BA.1] and 0.92 (0.79;1.06) [BA.2].

Interpretation

Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period.

Funding

UKRI, Wellcome Trust, MRC, NIHR and HDRUK.",,doi:https://doi.org/10.1101/2023.05.12.23289914; html:https://europepmc.org/article/PPR/PPR660616; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR660616&type=FILE&fileName=EMS175947-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/05/16/2023.05.12.23289914.full.pdf -PPR625199,https://doi.org/10.2139/ssrn.4322399,Baby and Maternal Outcomes Following SARS-CoV-2 Infection and COVID-19 Vaccination During Pregnancy: A National Population-Based Matched Cohort Study,"Lindsay L, Calvert C, Shi T, Carruthers J, Denny C, Donaghy J, Hopcroft LE, Hopkins L, Goulding A, McLaughlin T, Moore E, Taylor B, Bhaskaran K, Katikireddi SV, McCabe R, McCowan C, Simpson C, Robertson C, Sheikh A, Wood R, Stock SJ.",,No Journal Info,2023,2023-01-20,N,,,,"Background: Understanding the impact of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy on maternal and perinatal outcomes informs clinical decision-making.

Methods: We undertook a national, population-based, matched cohort study to investigate associations between SARS-CoV-2 infection and, separately, COVID-19 vaccination just before or during pregnancy and the risk of adverse baby and maternal outcomes among women in Scotland with a singleton pregnancy ending at ≥20 weeks gestation. Baby outcomes examined were stillbirth, neonatal death, extended perinatal mortality, preterm birth (overall, spontaneous, and provider-initiated), small-for-gestational age, and low Apgar score. Maternal outcomes were admission to critical care or death, venous thromboembolism, hypertensive disorders of pregnancy, and pregnancy-related bleeding. Conditional logistic regression models were used to derive odds ratios adjusted for socio-demographic and clinical characteristics (aORs) and 95% confidence intervals (CIs).

Findings: Our infection analyses of 4,074 women with confirmed SARS-CoV-2 infection matched on maternal age, season of conception, and gestational age at infection/matching to 12,222 uninfected controls, found that infection was associated with an increased risk of preterm (aOR=1·36, 95% CI 1·16-1·59) and very preterm birth (aOR=1·90, 95% CI 1·20-3·02), maternal admission to critical care or death (aOR=1·72, 95% CI 1·39-2·12), and venous thromboembolism (aOR=2·53, 95% CI 1·47-4·35). Our vaccination analyses found no evidence of increased risk for any baby or maternal outcomes following vaccination.InterpretationSARS-CoV-2 infection during pregnancy is associated with adverse baby and maternal outcomes, but COVID-19 vaccination is not. COVID-19 vaccination remains the safest way for pregnant women to protect themselves and their babies against SARS-CoV-2 infection.

Funding: Our thanks to the EAVE II Patient Advisory Group and Sands charity for their support. COPS is a sub-study of EAVE II, which is funded by the Medical Research Council (MC_PC_19075) with the support of BREATHE – The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommy’s charity. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17).

Declaration of Interests: AS and CR were members of the Scottish Government’s COVID-19 Advisory Group. AS is a member of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) risk stratification subgroup and the Scottish Government’s Committee on Pandemic Preparedness. CR is a member of the Scientific Pandemic Influenza Group on Modelling and the MHRA Covid 19 Vaccine Benefit and Risk Working Group. AS is a member of AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group. All roles are unremunerated. SVK was co-chair of Scottish Government’s Expert Reference Group on Ethnicity and COVID-19. All others have nothing to declare.

Ethics Approval: COPS has ethical approval from the National Research Ethics Service Committee, South East Scotland 02 (REC 12/SS/0201: SA 2) and information governance approval from the Public Benefit and Privacy Panel for Health and Social Care (2021-0116).",,doi:https://doi.org/10.2139/ssrn.4322399; html:https://europepmc.org/article/PPR/PPR625199; doi:https://doi.org/10.2139/ssrn.4322399 PPR279444,https://doi.org/10.1101/2021.02.07.21251297,The changing characteristics of COVID-19 presentations: A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave,"Atkin C, Kamwa V, Reddy-Kolanu V, Parekh D, Evison F, Nightingale P, Gallier S, Ball S, Sapey E.",,No Journal Info,2021,2021-02-08,Y,,,,"

Background

This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus.

Methods

All patients with a positive SARS-CoV-2 swab between 10 th March 2020 and 5 th July 2020 (wave 1) and 1 st September 2020 and 16 th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days.

Results

Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions.

Conclusion

Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.",,doi:https://doi.org/10.1101/2021.02.07.21251297; html:https://europepmc.org/article/PPR/PPR279444; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR279444&type=FILE&fileName=EMS116132-pdf.pdf&mimeType=application/pdf +PPR625199,https://doi.org/10.2139/ssrn.4322399,Baby and Maternal Outcomes Following SARS-CoV-2 Infection and COVID-19 Vaccination During Pregnancy: A National Population-Based Matched Cohort Study,"Lindsay L, Calvert C, Shi T, Carruthers J, Denny C, Donaghy J, Hopcroft LE, Hopkins L, Goulding A, McLaughlin T, Moore E, Taylor B, Bhaskaran K, Katikireddi SV, McCabe R, McCowan C, Simpson C, Robertson C, Sheikh A, Wood R, Stock SJ.",,No Journal Info,2023,2023-01-20,N,,,,"Background: Understanding the impact of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy on maternal and perinatal outcomes informs clinical decision-making.

Methods: We undertook a national, population-based, matched cohort study to investigate associations between SARS-CoV-2 infection and, separately, COVID-19 vaccination just before or during pregnancy and the risk of adverse baby and maternal outcomes among women in Scotland with a singleton pregnancy ending at ≥20 weeks gestation. Baby outcomes examined were stillbirth, neonatal death, extended perinatal mortality, preterm birth (overall, spontaneous, and provider-initiated), small-for-gestational age, and low Apgar score. Maternal outcomes were admission to critical care or death, venous thromboembolism, hypertensive disorders of pregnancy, and pregnancy-related bleeding. Conditional logistic regression models were used to derive odds ratios adjusted for socio-demographic and clinical characteristics (aORs) and 95% confidence intervals (CIs).

Findings: Our infection analyses of 4,074 women with confirmed SARS-CoV-2 infection matched on maternal age, season of conception, and gestational age at infection/matching to 12,222 uninfected controls, found that infection was associated with an increased risk of preterm (aOR=1·36, 95% CI 1·16-1·59) and very preterm birth (aOR=1·90, 95% CI 1·20-3·02), maternal admission to critical care or death (aOR=1·72, 95% CI 1·39-2·12), and venous thromboembolism (aOR=2·53, 95% CI 1·47-4·35). Our vaccination analyses found no evidence of increased risk for any baby or maternal outcomes following vaccination.InterpretationSARS-CoV-2 infection during pregnancy is associated with adverse baby and maternal outcomes, but COVID-19 vaccination is not. COVID-19 vaccination remains the safest way for pregnant women to protect themselves and their babies against SARS-CoV-2 infection.

Funding: Our thanks to the EAVE II Patient Advisory Group and Sands charity for their support. COPS is a sub-study of EAVE II, which is funded by the Medical Research Council (MC_PC_19075) with the support of BREATHE – The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommy’s charity. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17).

Declaration of Interests: AS and CR were members of the Scottish Government’s COVID-19 Advisory Group. AS is a member of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) risk stratification subgroup and the Scottish Government’s Committee on Pandemic Preparedness. CR is a member of the Scientific Pandemic Influenza Group on Modelling and the MHRA Covid 19 Vaccine Benefit and Risk Working Group. AS is a member of AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group. All roles are unremunerated. SVK was co-chair of Scottish Government’s Expert Reference Group on Ethnicity and COVID-19. All others have nothing to declare.

Ethics Approval: COPS has ethical approval from the National Research Ethics Service Committee, South East Scotland 02 (REC 12/SS/0201: SA 2) and information governance approval from the Public Benefit and Privacy Panel for Health and Social Care (2021-0116).",,doi:https://doi.org/10.2139/ssrn.4322399; html:https://europepmc.org/article/PPR/PPR625199; doi:https://doi.org/10.2139/ssrn.4322399 PPR661573,https://doi.org/10.21203/rs.3.rs-2846109/v1,Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses,"Michael B, Dunai C, Needham E, Tharmaratnam K, Williams R, Huang Y, Boardman S, Clark J, Sharma P, Subramaniam K, Wood G, Collie C, Digby R, Ren A, Norton E, Leibowitz M, Ebrahimi S, Fower A, Fox H, Tato E, Ellul M, Sunderland G, Held M, Hetherington C, Egbe F, Palmos A, Stirrups K, Grundmann A, Stewart J, Griffiths M, Solomon T, Breen G, Coles A, Cavanagh J, Irani S, Vincent A, Baillie J, Openshaw P, Semple M, corsortium C, Taams L, Menon D, ISARIC-4C Investigators.",,No Journal Info,2023,2023-05-17,Y,,,,"Neurological complications occur in a significant proportion of COVID-19 cases. In order to identify key biomarkers, we measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants admitted to hospital for management of COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided convalescent sera (up to76 weeks post admission). Compared to 60 controls, brain injury biomarkers (total-Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in participants with altered consciousness. Total-Tau (tTau) and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness and correlated with brain injury biomarker levels. Inflammatory mediators were lower in convalescent sera than acute sera. Levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with tTau levels even at later time points. When compared to acute COVID-19 patients with a normal Glasgow Coma Scale score (GCS), network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase of COVID-19 and we found brain injury markers persist during convalescence and may be driven by a para-infectious process involving a dysregulated host response.",,doi:https://doi.org/10.21203/rs.3.rs-2846109/v1; html:https://europepmc.org/article/PPR/PPR661573; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR661573&type=FILE&fileName=EMS175982-pdf.pdf&mimeType=application/pdf PPR605762,https://doi.org/10.2139/ssrn.4224500,Neutralising Antibody Potency Against SARS-CoV-2 Ancestral and Omicron BA.1 and BA.4/5 Variants in Patients with Inflammatory Bowel Disease after Three Doses of COVID-19 Vaccine: A Prospective Multicentre Cohort Study (CLARITY),"Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald T, Lamb CA, Sebastian S, Kok K, Lees C, Altmann D, Hart A, Boyton RJ, Pollock KM, Goodhand J, Kennedy NA, Ahmad T, Powell N.",,No Journal Info,2022,2022-09-21,N,,,,"Background: Anti-tumour necrosis factor (TNF) drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination. It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection.

Methods: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the impact of infliximab and vedolizumab, a gut-specific anti-integrin monoclonal antibody, on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). The primary outcome was neutralising antibody responses against SARS-CoV-2 ancestral and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres.

Findings: Following three doses of COVID-19 vaccine, neutralising antibody NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against ancestral (geometric mean [95% CI], 1990 [1781 to 2223] vs 3212 [2780 to 3712], p<0·0001), BA.1 (95·46 [82·80 to 110·0] vs 599·1 [492·6 to 728·6], p<0·0001) and BA.4/5 (30·73 [26·26 to 35·96] vs 212·2 [177·0 to 254·4], p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (13·66%, [11·49% to 16·16%], 119/871) compared to patients treated with vedolizumab (6·95%, [4·79% to 9·95%], 29/417, p=0·0004). Cox proportional hazards models of time to breakthrough infection after the third dose showed infliximab treatment to be associated with a higher hazard risk of 1·71 [1·08 to 2·71] p=0·022) compared to vedolizumab. Higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and a longer time to breakthrough infection (HR 0·91 [0·84 to 0·99] p=0·030).

Interpretation: Following a third COVID-19 vaccine dose, patients established on infliximab treatment have significantly lower neutralising titres against SARS-CoV-2, which were especially low against Omicron variants. Increased breakthrough infection in infliximab recipients was associated with lower neutralising antibody levels against BA.4/5. These data underline the importance of continued COVID-19 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy may be reduced.

Trial Registration Details: The study was registered with the ISRCTN registry ISRCTN45176516 and the protocol is available online at https://www.clarityibd.org.

Funding Information: Royal Devon and Exeter NHS Foundation Trust, Hull University Teaching Hospital NHS Trust, NIHR Imperial Biomedical Research Centre, Crohn’s and Colitis UK (M2021/1), Guts UK, NCSi programme UKRI (award to RB, DA, NP and TA, MR/W020610/1) and unrestricted educational grants from F. Hoffmann-La Roche (Switzerland), Biogen (USA), Celltrion Healthcare (South Korea), Takeda (UK) and Galapagos (Belgium).

Declaration of Interests: SL reports non-financial support from Pfizer, non-financial support from Ferring outside the submitted work. JLA reports sponsorship from Vifor Pharma for accommodation and travel to the British Society of Gastroenterology annual meeting 2019, outside the submitted work. NAK reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; grants and non-financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non-financial support from Janssen and Dr Falk, personal fees from Takeda, outside the submitted work. SS reports grants from Takeda, AbbVie, Tillots Pharma, Janssen, Pfizer, and Biogen, and personal fees from Takeda, AbbVie, Janssen, Pharmacocosmos, Biogen, Pfizer, Tillots Pharma, and Falk Pharma, outside the submitted work. ALH reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, AZ, Atlantic, Bristol Myers Squibb, Celltrion, Falk, Galapogos, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire, and Takeda; participation on the Global Steering Committee for Genentech; support for attending meetings from AbbVie, Takeda, and Janssen; and participation on a data safety monitoring board or advisory board for AbbVie, AZ, Atlantic, Bristol Myers Squibb, Galapogos, Janssen, Pfizer, and Takeda. KK reports payment or honoraria for lectures, presentations personal fees from Takeda, Janssen, Pfizer, Galapagos, Bristol Myers Squibb, AbbVie, Roche, Lilly, Allergan, and Celgene, Astra Zeneca outside the submitted work; and has served as a speaker or advisory board member for AbbVie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda, and Vifor
Pharma. All other authors declare no competing interests.


Ethics Approval Statement: The Surrey Borders Research Ethics committee approved the study (REC reference: 20/HRA/3114) in September 2020. Patients were included after providing informed, written consent.",,doi:https://doi.org/10.2139/ssrn.4224500; html:https://europepmc.org/article/PPR/PPR605762; doi:https://doi.org/10.2139/ssrn.4224500 PPR293775,https://doi.org/10.1101/2021.03.04.21252931,A common TMPRSS2 variant protects against severe COVID-19,"David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, Casanova J, Abel L, Barclay WS, Baillie JK, Sternberg MJ, GenOMICC Investigators, ISARIC4C Investigators.",,No Journal Info,2021,2021-03-08,Y,,,,"

Summary

Infection with SARS-CoV-2 has a wide range of clinical presentations, from asymptomatic to life-threatening. Old age is the strongest factor associated with increased COVID19-related mortality, followed by sex and pre-existing conditions. The importance of genetic and immunological factors on COVID19 outcome is also starting to emerge, as demonstrated by population studies and the discovery of damaging variants in genes controlling type I IFN immunity and of autoantibodies that neutralize type I IFNs. The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus’ spike protein, facilitating entry into target cells. We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760), which has a minor allele frequency of ∼25% in the population. In a large population of SARS-CoV-2 positive patients, we show that this variant is associated with a reduced likelihood of developing severe COVID19 (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3×10 −3 ). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, impacts the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells. TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID19. Further studies are needed to assess the expression of the TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID19. Clinical trials are needed to confirm this.",,doi:https://doi.org/10.1101/2021.03.04.21252931; html:https://europepmc.org/article/PPR/PPR293775; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR293775&type=FILE&fileName=EMS118903-pdf.pdf&mimeType=application/pdf @@ -28,8 +28,8 @@ PPR557473,https://doi.org/10.1101/2022.10.12.22281016,Quantifying changes in the PPR625471,https://doi.org/10.2139/ssrn.4376992,Identifying Long Covid Using Electronic Health Records: A National Observational Cohort Study in Scotland,"Jeffrey K, Woolford L, Maini R, Basetti S, Batchelor A, Weatherill D, White C, Hammersley V, Millington T, Macdonald C, Quint J, Kerr R, Kerr S, Shah SA, Fagbamigbe AF, Simpson C, Katikireddi SV, Robertson C, Ritchie LD, Sheikh A, Daines L.",,No Journal Info,2023,2023-03-07,N,,,,"Background: Long COVID is a debilitating multisystem condition. To estimate prevalence and identify risk factors, we analysed routinely collected data from almost the entire adult population of Scotland.

Methods: A cohort of adults (≥18 years) resident in Scotland between March 1, 2020, and October 20, 2022, was created by linking data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The latter was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2.

Findings: Of 5,104,198 participants, 90,712 (1·8%) were identified as having long COVID by one or more outcome measures. Clinical codes were rarely recorded (n=1,092, 0·02%). More people were identified using free text (n= 8,368, 0·2%), sick notes (n=14,471, 0·3%) and the operational definition (n=73,767, 1·4%). Compared with the general population, a higher proportion of people with long COVID were female, middle-aged, overweight/obese, had at least two comorbidities, were immunosuppressed, shielding, or hospitalised within 28 days of testing positive, and had tested positive before Omicron became the dominant variant.

Interpretation: The prevalence of long COVID presenting in general practice was estimated to be 0·02 - 1·8%, depending on the measure used. Of the four outcome measures used, clinical codes identified the fewest cases. With limited use of long COVID clinical codes, we consider free text analysis to be the most promising approach should future surveillance of long COVID at a national level be required.

Funding: Chief Scientist Office (Scotland) and Medical Research Council.

Declaration of Interest: AS reports grants from HDRUK, grants from NIHR, grants from MRC, grants from ICSF, during the conduct of the study; and Member of Scottish Government's CMO COVID-19 Advisory Group and Standing Committee on Pandemics. CR reports support from PHS and MRC. CS reports grants from MBIE (New Zealand), Ministry of Health (New Zealand), and HRC (New Zealand). JKQ reports grants from MRC, HDR UK, GlaxoSmithKline, BI, Asthma+Lung UK, and AstraZeneca and consulting fees from GlaxoSmithKline, Evidera, AstraZeneca, Insmed. All other authors declare no competing interests.

Ethical Approval: The EAVE II study obtained approvals from the West of Scotland Research Ethics Committee (reference: 22/WS/0071), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279).",,doi:https://doi.org/10.2139/ssrn.4376992; html:https://europepmc.org/article/PPR/PPR625471; doi:https://doi.org/10.2139/ssrn.4376992 PPR215604,https://doi.org/10.1101/2020.09.17.20196469,Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care,"Haroon S, Subramanian A, Cooper J, Anand A, Gokhale K, Byne N, Dhalla S, Acosta-Mena D, Taverner T, Okoth K, Wang J, Chandan JS, Sainsbury C, Zemedikun DT, Thomas GN, Parekh D, Marshall T, Sapey E, Adderley NJ, Nirantharakumar K.",,No Journal Info,2020,2020-09-18,Y,,,,"

Introduction

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

Methods

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

Results

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

Conclusion

Current use of ACE inhibitors was not associated with the risk of suspected or confirmed COVID-19 whereas use of ARBs was associated with a statistically non-significant 38% relative increase in risk compared to use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality during the peak of the pandemic.",,doi:https://doi.org/10.1101/2020.09.17.20196469; html:https://europepmc.org/article/PPR/PPR215604; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR215604&type=FILE&fileName=EMS96164-pdf.pdf&mimeType=application/pdf PPR686624,https://doi.org/10.1101/2023.07.03.23291596,Risk of COVID-19 death in adults who received booster COVID-19 vaccinations: national retrospective cohort study on 14.6 million people in England,"Ward I, Robertson C, Agrawal U, Patterson L, Bradley DT, Shi T, Lusignan Sd, Hobbs R, Sheikh A, Nafilyan V.",,No Journal Info,2023,2023-07-05,Y,,,,"

Importance

The emergence of the COVID-19 vaccination has been critical in changing the course of the COVID-19 pandemic, with estimates suggesting vaccinations have prevented millions of deaths worldwide. To ensure protection remains high in vulnerable groups booster vaccinations in the UK have been targeted based on age and clinical vulnerabilities.

Objective

We sought to identify adults who had received a booster vaccination as part of the autumn 2022 campaign in England yet remained at increased risk of postbooster COVID-19 death and compared to non-COVID-19 risk.

Design, Setting, and Participants

We undertook a national retrospective cohort study using data from the 2021 Census linked to electronic health records. We fitted cause-specific Cox models to examine the association between health conditions and the risk of COVID-19 death and all-other-cause death for adults aged 50-100-years in England vaccinated with a booster in autumn 2022. Our total population was 14,644,570 people; there were 6,800 COVID-19 deaths and 150,075 non-COVID-19 deaths.

Exposure

Sociodemographic characteristics (sex, age, ethnic group, region), disability, body mass index, and diagnosis of a health condition defined from QCovid2.

Main Outcomes and Measures

The primary outcome of this study was COVID-19 death. The secondary outcome was all-cause non-COVID-19 deaths.

Results

Having learning disabilities or Down Syndrome (hazard ratio=5.07;95% confidence interval=3.69-6.98), pulmonary hypertension or fibrosis (2.88;2.43-3.40), motor neuron disease, multiple sclerosis, myasthenia or Huntington’s disease (2.94, 1.82-4.74), cancer of blood and bone marrow (3.11;2.72-3.56), Parkinson’s disease (2.74;2.34-3.20), lung or oral cancer (2.57;2.04 to 3.24), dementia (2.64;2.46 to 2.83) or liver cirrhosis (2.65;1.95 to 3.59) was associated with an increased risk of COVID-19 death. Individuals with cancer of the blood or bone marrow, chronic kidney disease, cystic fibrosis, pulmonary hypotension or fibrosis, or rheumatoid arthritis or systemic lupus erythematosus had a significantly higher risk of COVID-19 death relative to other causes of death compared with individuals who did not have diagnoses.

Conclusions, and Relevance

We identify groups who are at increased risk of postbooster COVID-19 death relative to non-COVID-19 deaths. Policy makers should continue to priorities vulnerable groups for subsequent COVID-19 booster doses to minimise the risk of COVID-19 death.

Funding

National Core Studies–Immunity, National Core Studies–Data and Connectivity, Health Data Research UK, and the Medical Research Council .

Key Points

Question: What health conditions are associated with increased risk of postbooster COVID-19 death in adults who received a COVID-19 vaccination in autumn 2022?

Findings:

Certain groups were found to be at overall higher risk of postbooster COVID-19 death (e.g., learning disability or Down Syndrome) and certain groups were found to have significantly higher relative risk of COVID-19 death compared to other non-COVID-19 causes (e.g., cancer of the blood or bone marrow). Meaning: This work has implications for prioritisation of vaccination booster doses worldwide. We highlight which groups with health conditions are at elevated risk of postbooster COVID-19 death.",,doi:https://doi.org/10.1101/2023.07.03.23291596; html:https://europepmc.org/article/PPR/PPR686624; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR686624&type=FILE&fileName=EMS178585-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/07/05/2023.07.03.23291596.full.pdf -PPR592803,https://doi.org/10.1101/2023.01.04.22283762,Challenges in estimating waning effectiveness of two doses of BNT162b2 and ChAdOx1 COVID-19 vaccines beyond six months: an OpenSAFELY cohort study using linked electronic health records,"Horne EM, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EP, Walker VM, Knight R, Wei Y, Taylor K, Fisher L, Morley J, Mehrkar A, Dillingham I, Bacon S, Goldacre B, Sterne JA, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-01-05,Y,,,,"Quantifying the waning effectiveness of second COVID-19 vaccination beyond six months and against the omicron variant is important for scheduling subsequent doses. With the approval of NHS England, we estimated effectiveness up to one year after second dose, but found that bias in such estimates may be substantial.",,doi:https://doi.org/10.1101/2023.01.04.22283762; html:https://europepmc.org/article/PPR/PPR592803; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR592803&type=FILE&fileName=EMS159412-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/05/2023.01.04.22283762.full.pdf PPR497639,https://doi.org/10.1101/2022.05.21.22275368,"Variant-specific symptoms of COVID-19 among 1,542,510 people in England","Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott P.",,No Journal Info,2022,2022-05-23,Y,,,,"Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.",,doi:https://doi.org/10.1101/2022.05.21.22275368; html:https://europepmc.org/article/PPR/PPR497639; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR497639&type=FILE&fileName=EMS145381-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/23/2022.05.21.22275368.full.pdf +PPR592803,https://doi.org/10.1101/2023.01.04.22283762,Challenges in estimating waning effectiveness of two doses of BNT162b2 and ChAdOx1 COVID-19 vaccines beyond six months: an OpenSAFELY cohort study using linked electronic health records,"Horne EM, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EP, Walker VM, Knight R, Wei Y, Taylor K, Fisher L, Morley J, Mehrkar A, Dillingham I, Bacon S, Goldacre B, Sterne JA, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-01-05,Y,,,,"Quantifying the waning effectiveness of second COVID-19 vaccination beyond six months and against the omicron variant is important for scheduling subsequent doses. With the approval of NHS England, we estimated effectiveness up to one year after second dose, but found that bias in such estimates may be substantial.",,doi:https://doi.org/10.1101/2023.01.04.22283762; html:https://europepmc.org/article/PPR/PPR592803; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR592803&type=FILE&fileName=EMS159412-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/05/2023.01.04.22283762.full.pdf PPR539139,https://doi.org/10.1101/2022.09.01.22279473,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK),"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe DA, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,No Journal Info,2022,2022-09-02,Y,,,,"

ABSTRACT

Background

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

Methods

We conducted a population-based longitudinal study in 2,312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and moderate/severe asthma exacerbations were collected via monthly on-line questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.

Results

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

Conclusions

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

Funding

Barts Charity, UKRI",,doi:https://doi.org/10.1101/2022.09.01.22279473; html:https://europepmc.org/article/PPR/PPR539139; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR539139&type=FILE&fileName=EMS153770-pdf.pdf&mimeType=application/pdf PPR517024,https://doi.org/,Brazilian COVID-19 data streaming,"Silva NBd, Valencia LIO, Filho FMHS, Ferreira ACS, Pereira FAC, Oliveira GLd, Oliveira PF, Rodrigues MS, Ramos PIP, Oliveira JF.",,No Journal Info,2022,2022-05-10,Y,,,,"We collected individualized (unidentifiable) and aggregated openly available data from various sources related to suspected/confirmed SARS-CoV-2 infections, vaccinations, non-pharmaceutical government interventions, human mobility, and levels of population inequality in Brazil. In addition, a data structure allowing real-time data collection, curation, integration, and extract-transform-load processes for different objectives was developed. The granularity of this dataset (state- and municipality-wide) enables its application to individualized and ecological epidemiological studies, statistical, mathematical, and computational modeling, data visualization as well as the scientific dissemination of information on the COVID-19 pandemic in Brazil.",,arxiv:https://arxiv.org/abs/2205.05032v1; html:https://europepmc.org/article/PPR/PPR517024; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR517024&type=FILE&fileName=EMS150464-pdf.pdf&mimeType=application/pdf PPR503564,https://doi.org/10.1101/2022.06.07.22276080,"Non-pharmacological therapies for post-viral syndromes, including Long COVID: A systematic review","Chandan JS, Brown KR, Simms-Williams N, Bashir NZ, Camaradou J, Heining D, Turner GM, Rivera SC, Hotham R, Minhas S, Niratharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Marshall T, Calvert MJ, Haroon S, Aiyegbusi OL.",,No Journal Info,2022,2022-06-07,Y,,,,"

Background

Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises evidence for the effectiveness of non-pharmacological treatments for symptoms of PVS. It also summarises the symptoms and health impacts of PVS in individuals recruited to studies evaluating treatments.

Methods and findings

We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 st January 2001 to 29 th October 2021. We anticipated that there would be few RCTs specifically pertaining to Long COVID, so we also included observational studies only if they assessed interventions in individuals where the viral pathogen was SARS-COV-2. Relevant outcome data were extracted, study quality appraised using the Cochrane Risk of Bias tool, and the findings were synthesised narratively. Quantitative synthesis was not planned due to substantial heterogeneity between the studies. Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.

Conclusions

In this study, we observed a lack of robust evidence evaluating non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS as well as what may work for certain sub-groups of patients with differential symptom presentation.

Registration

The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Author summary

Why was this study done? The prevalence of Long COVID following exposure to SARS CoV-2 is substantial, and the current guidance provides few evidence-based treatment options for clinicians to suggest to their patients. Due to the similarities in presentation of other post-viral syndromes (PVS), and the lack of consensus in management approaches, there is a need to synthesise the available data on PVS to both support patients with PVS predating the pandemic, and those with Long COVID. What did the researchers do and find? This is the first comprehensive systematic review of the effectiveness of non-pharmacological treatments for patients with PVS, including Long COVID. We identified four non-pharmacological treatments (Pilates, telerehabilitation, resistance exercises and neuromodulation) which have shown promise in those who have experienced signs and symptoms related to PVS. What do these findings mean? In this study, we identified few trials assessing the effectiveness of non-pharmacological therapies to support the management of symptoms of PVS. Considering the prevalence of PVS, including Long COVID, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological therapies to support these patients.",,doi:https://doi.org/10.1101/2022.06.07.22276080; html:https://europepmc.org/article/PPR/PPR503564; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR503564&type=FILE&fileName=EMS162209-pdf.pdf&mimeType=application/pdf @@ -50,8 +50,8 @@ PPR519618,https://doi.org/10.1101/2022.07.15.22277678,Influence of vitamin D sup PPR384241,https://doi.org/10.1101/2021.08.13.21261889,Robust SARS-CoV-2-specific and heterologous immune responses after natural infection in elderly residents of Long-Term Care Facilities,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Margielewska-Davies S, Verma K, Nicol S, Begum J, Blakeway D, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,No Journal Info,2021,2021-08-18,Y,,,,"Long term care facilities (LTCF) provide residential and/or nursing care support for frail and elderly people and many have suffered from a high prevalence of SARS-CoV-2 infection. Although mortality rates have been high in LTCF residents there is little information regarding the features of SARS-CoV-2-specific immunity after infection in this setting or how this may influence immunity to other infections. We studied humoral and cellular immunity against SARS-CoV-2 in 152 LTCF staff and 124 residents over a prospective 4-month period shortly after the first wave of infection and related viral serostatus to heterologous immunity to other respiratory viruses and systemic inflammatory markers. LTCF residents developed high levels of antibodies against spike protein and RBD domain which were stable over 4 months of follow up. Nucleocapsid-specific responses were also elevated in elderly donors but showed waning across all populations. Antibodies showed stable and equivalent levels of functional inhibition against spike-ACE2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or RSV. SARS-CoV-2-specific cellular responses were equivalent across the life course but virus-specific populations showed elevated levels of activation in older donors. LTCF residents who are survivors of SARS-CoV-2 infection thus show robust and stable immunity which does not impact responses to other seasonal viruses. These findings augur well for relative protection of LTCF residents to re-infection. Furthermore, they underlie the potent influence of previous infection on the immune response to Covid-19 vaccine which may prove to be an important determinant of future vaccine strategy.

One sentence summery

Care home residents show waning of nucleocapsid specific antibodies and enhanced expression of activation markers on SARS-CoV-2 specific cells",,doi:https://doi.org/10.1101/2021.08.13.21261889; html:https://europepmc.org/article/PPR/PPR384241; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR384241&type=FILE&fileName=EMS133205-pdf.pdf&mimeType=application/pdf PPR555346,https://doi.org/10.21203/rs.3.rs-2129185/v1,COVID-19 vaccination and SARS-CoV-2 infection in early pregnancy and the risk of major congenital anomalies: a national population-based cohort study,"Wood R, Calvert C, Carruthers J, Denny C, Donaghy J, Hopcoft L, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Taylor J, Loane M, Dolk H, Morris J, Auyeung B, Bhaskaran K, Gibbons C, Katikireddi S, O’Leary M, McAllister D, Shi T, Simpson C, Robertson C, Sheikh A, Stock S.",,No Journal Info,2022,2022-10-06,Y,,,,"Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. We conducted a national, population-based, matched cohort study to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any congenital anomaly and; [2] non-genetic anomalies. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6,731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any congenital anomaly and 120 had a non-genetic anomaly. Primary analyses found no association between vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83–1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81–1.22). Primary analyses also found no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66–1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57–1.54). Findings were robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.",,doi:https://doi.org/10.21203/rs.3.rs-2129185/v1; html:https://europepmc.org/article/PPR/PPR555346; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR555346&type=FILE&fileName=EMS155419-pdf.pdf&mimeType=application/pdf; pdf:https://www.nature.com/articles/s41467-022-35771-8.pdf PPR445332,https://doi.org/10.1101/2022.01.21.22269651,"Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK","Marchant E, Lowthian E, Crick T, Griffiths L, Fry R, Dadaczynski K, Okan O, James M, Cowley L, Torabi F, Kennedy J, Akbari A, Lyons R, Brophy S.",,No Journal Info,2022,2022-01-22,Y,,,,"

ABSTRACT

Objectives

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

Design

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

Setting

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

Participants

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

Main outcome measures

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

Results

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

Conclusions

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

STRENGTHS AND LIMITATIONS

Investigation of the association of pre-pandemic child health-related behaviour measures with subsequent SARS-CoV-2 testing and infection. Reporting of multiple child health behaviours linked at an individual-level to routine records of SARS-CoV-2 testing data through the SAIL Databank. Child-reported health behaviours were measured before the COVID-19 pandemic (1 January 2018 to 28 February 2020) which may not reflect behaviours during COVID-19. Health behaviours captured through the national-scale HAPPEN survey represent children attending schools that engaged with the HAPPEN Wales primary school network and may not be representative of the whole population of Wales. The period of study for PCR-testing for and testing positive for SARS-CoV-2 includes a time frame with varying prevalence rates, approaches to testing children (targeted and mass testing) and restrictions which were not measured in this study.",,doi:https://doi.org/10.1101/2022.01.21.22269651; html:https://europepmc.org/article/PPR/PPR445332; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR445332&type=FILE&fileName=EMS142585-pdf.pdf&mimeType=application/pdf -PPR618591,https://doi.org/10.1101/2023.02.18.23286127,Antipsychotic prescribing and mortality in people with dementia before and during the COVID-19 pandemic: retrospective cohort study,"Schnier C, McCarthy A, Morales DR, Akbari A, Sofat R, Dale C, Takhar R, Mamas MA, Khunti K, Zaccardi F, Sudlow CL, Wilkinson T.",,No Journal Info,2023,2023-02-19,Y,,,,"

ABSTRACT

Background

Antipsychotic drugs have been associated with increased mortality, stroke and myocardial infarction in people with dementia. Concerns have been raised that antipsychotic prescribing may have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of the virus. We used multisource, routinely-collected healthcare data from Wales, UK, to investigate prescribing and mortality trends in people with dementia before and during the COVID-19 pandemic.

Methods

We used individual-level, anonymised, population-scale linked health data to identify adults aged ≥60 years with a diagnosis of dementia in Wales, UK. We explored antipsychotic prescribing trends over 67 months between 1 st January 2016 and 1 st August 2021, overall and stratified by age and dementia subtype. We used time series analyses to examine all-cause, myocardial infarction (MI) and stroke mortality over the study period and identified the leading causes of death in people with dementia.

Findings

Of 57,396 people with dementia, 11,929 (21%) were prescribed an antipsychotic at any point during follow-up. Accounting for seasonality, antipsychotic prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 to 1305 per 10,000 person-months. Prescribing in the 60-64 age group and those with Alzheimer’s disease increased throughout the 5-year period. All-cause and stroke mortality increased in the second half of 2019 and throughout 2020 but MI mortality declined. From January 2020, COVID-19 was the second commonest underlying cause of death in people with dementia.

Interpretation

During the COVID-19 pandemic there was a small increase in antipsychotic prescribing in people with dementia. The long-term increase in antipsychotic prescribing in younger people and in those with Alzheimer’s disease warrants further investigation.

Funding

British Heart Foundation (BHF) (SP/19/3/34678) via the BHF Data Science Centre led by HDR UK, and the Scottish Neurological Research Fund.

Research in Context

Evidence before this study

We searched Ovid MEDLINE for studies describing antipsychotic prescribing trends in people with dementia during the COVID-19 pandemic, published between 1st January 2020 and 22nd March 2022. The following search terms were used: (exp Antipsychotic Agents/ OR antipsychotic.mp OR neuroleptic.mp OR risperidone.mp OR exp Risperidone/ OR quetiapine.mp OR exp Quetiapine Fumarate/ OR olanzapine.mp OR exp Olanzapine/ OR exp Psychotropic Drugs/ or psychotropic.mp) AND (exp Dementia/ OR exp Alzheimer Disease/ or alzheimer.mp) AND (prescri*.mp OR exp Prescriptions/ OR exp Electronic Prescribing/ OR trend*.mp OR time series.mp). The search identified 128 published studies, of which three were eligible for inclusion. Two studies, based on data from England and the USA, compared antipsychotic prescribing in people with dementia before and during the COVID-19 pandemic. Both reported an increase in the proportion of patients prescribed an antipsychotic after the onset of the pandemic. A third study, based in the Netherlands, reported antipsychotic prescription trends in nursing home residents with dementia during the first four months of the pandemic, comparing prescribing rates to the timings of lifting of social restrictions, showing that antipsychotic prescribing rates remained constant throughout this period.

Added value of this study

We conducted age-standardised time series analyses using comprehensive, linked, anonymised, individual-level routinely-collected, population-scale health data for the population of Wales, UK. By accounting for seasonal variations in prescribing and mortality, we demonstrated that the absolute increase in antipsychotic prescribing in people with dementia of any cause during the COVID-19 pandemic was small. In contrast, antipsychotic prescribing in the youngest age group (60-64 years) and in people with a subtype diagnosis of Alzheimer’s disease increased throughout the five-year study period. Accounting for seasonal variation, all-cause mortality rates in people with dementia began to increase in late 2019 and increased sharply during the first few months of the pandemic. COVID-19 became the leading non-dementia cause of death in people with dementia from 2020 to 2021. Stroke mortality increased during the pandemic, following a similar pattern to that of all-cause mortality, whereas myocardial infarction rates decreased.

Implications of all the available evidence

During COVID-19 we observed a large increase in all-cause and stroke mortality in people with dementia. When seasonal variations are accounted for, antipsychotic prescribing rates in all-cause dementia increased by a small amount before and during the pandemic in the UK. The increased prescribing rates in younger age groups and in people with Alzheimer’s disease warrants further investigation.",,doi:https://doi.org/10.1101/2023.02.18.23286127; html:https://europepmc.org/article/PPR/PPR618591; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR618591&type=FILE&fileName=EMS170574-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/02/19/2023.02.18.23286127.full.pdf PPR530735,https://doi.org/10.1101/2022.08.08.22278576,Outcome of COVID-19 in hospitalised immunocompromised patients: an analysis of the WHO ISARIC CCP-UK prospective cohort study,"Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJ, Harrison EM, Baillie JK, Semple MG, Docherty AB, ISARIC4C investigators.",,No Journal Info,2022,2022-08-11,Y,,,,"

Background

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

Methods

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

Findings

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

Conclusions

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

Funding

National Institute for Health Research; Medical Research Council; Chief Scientist Office, Scotland.",,doi:https://doi.org/10.1101/2022.08.08.22278576; html:https://europepmc.org/article/PPR/PPR530735; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR530735&type=FILE&fileName=EMS152614-pdf.pdf&mimeType=application/pdf; pdf:https://www.pure.ed.ac.uk/ws/files/343951294/journal.pmed.1004086.pdf +PPR618591,https://doi.org/10.1101/2023.02.18.23286127,Antipsychotic prescribing and mortality in people with dementia before and during the COVID-19 pandemic: retrospective cohort study,"Schnier C, McCarthy A, Morales DR, Akbari A, Sofat R, Dale C, Takhar R, Mamas MA, Khunti K, Zaccardi F, Sudlow CL, Wilkinson T.",,No Journal Info,2023,2023-02-19,Y,,,,"

ABSTRACT

Background

Antipsychotic drugs have been associated with increased mortality, stroke and myocardial infarction in people with dementia. Concerns have been raised that antipsychotic prescribing may have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of the virus. We used multisource, routinely-collected healthcare data from Wales, UK, to investigate prescribing and mortality trends in people with dementia before and during the COVID-19 pandemic.

Methods

We used individual-level, anonymised, population-scale linked health data to identify adults aged ≥60 years with a diagnosis of dementia in Wales, UK. We explored antipsychotic prescribing trends over 67 months between 1 st January 2016 and 1 st August 2021, overall and stratified by age and dementia subtype. We used time series analyses to examine all-cause, myocardial infarction (MI) and stroke mortality over the study period and identified the leading causes of death in people with dementia.

Findings

Of 57,396 people with dementia, 11,929 (21%) were prescribed an antipsychotic at any point during follow-up. Accounting for seasonality, antipsychotic prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 to 1305 per 10,000 person-months. Prescribing in the 60-64 age group and those with Alzheimer’s disease increased throughout the 5-year period. All-cause and stroke mortality increased in the second half of 2019 and throughout 2020 but MI mortality declined. From January 2020, COVID-19 was the second commonest underlying cause of death in people with dementia.

Interpretation

During the COVID-19 pandemic there was a small increase in antipsychotic prescribing in people with dementia. The long-term increase in antipsychotic prescribing in younger people and in those with Alzheimer’s disease warrants further investigation.

Funding

British Heart Foundation (BHF) (SP/19/3/34678) via the BHF Data Science Centre led by HDR UK, and the Scottish Neurological Research Fund.

Research in Context

Evidence before this study

We searched Ovid MEDLINE for studies describing antipsychotic prescribing trends in people with dementia during the COVID-19 pandemic, published between 1st January 2020 and 22nd March 2022. The following search terms were used: (exp Antipsychotic Agents/ OR antipsychotic.mp OR neuroleptic.mp OR risperidone.mp OR exp Risperidone/ OR quetiapine.mp OR exp Quetiapine Fumarate/ OR olanzapine.mp OR exp Olanzapine/ OR exp Psychotropic Drugs/ or psychotropic.mp) AND (exp Dementia/ OR exp Alzheimer Disease/ or alzheimer.mp) AND (prescri*.mp OR exp Prescriptions/ OR exp Electronic Prescribing/ OR trend*.mp OR time series.mp). The search identified 128 published studies, of which three were eligible for inclusion. Two studies, based on data from England and the USA, compared antipsychotic prescribing in people with dementia before and during the COVID-19 pandemic. Both reported an increase in the proportion of patients prescribed an antipsychotic after the onset of the pandemic. A third study, based in the Netherlands, reported antipsychotic prescription trends in nursing home residents with dementia during the first four months of the pandemic, comparing prescribing rates to the timings of lifting of social restrictions, showing that antipsychotic prescribing rates remained constant throughout this period.

Added value of this study

We conducted age-standardised time series analyses using comprehensive, linked, anonymised, individual-level routinely-collected, population-scale health data for the population of Wales, UK. By accounting for seasonal variations in prescribing and mortality, we demonstrated that the absolute increase in antipsychotic prescribing in people with dementia of any cause during the COVID-19 pandemic was small. In contrast, antipsychotic prescribing in the youngest age group (60-64 years) and in people with a subtype diagnosis of Alzheimer’s disease increased throughout the five-year study period. Accounting for seasonal variation, all-cause mortality rates in people with dementia began to increase in late 2019 and increased sharply during the first few months of the pandemic. COVID-19 became the leading non-dementia cause of death in people with dementia from 2020 to 2021. Stroke mortality increased during the pandemic, following a similar pattern to that of all-cause mortality, whereas myocardial infarction rates decreased.

Implications of all the available evidence

During COVID-19 we observed a large increase in all-cause and stroke mortality in people with dementia. When seasonal variations are accounted for, antipsychotic prescribing rates in all-cause dementia increased by a small amount before and during the pandemic in the UK. The increased prescribing rates in younger age groups and in people with Alzheimer’s disease warrants further investigation.",,doi:https://doi.org/10.1101/2023.02.18.23286127; html:https://europepmc.org/article/PPR/PPR618591; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR618591&type=FILE&fileName=EMS170574-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/02/19/2023.02.18.23286127.full.pdf PPR534199,https://doi.org/10.21203/rs.3.rs-1955486/v1,Early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection: a national population-based matched cohort study,"Stock* S, Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcoft L, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Pan J, Taylor J, Almaghrabi F, Auyeung B, Bhaskaran K, Gibbons C, Katikireddi S, McCowan C, Murray J, O’Leary M, Ritchie L, Shah S, Simpson C, Robertson C, Sheikh A, Wood R.",,No Journal Info,2022,2022-08-19,Y,,,,"There are limited data regarding the safety of COVID-19 vaccines in early pregnancy. This may contribute to vaccine hesitancy in people who are pregnant, or who are planning pregnancy. We conducted a population-level matched cohort study assessing associations between COVID-19 vaccination and miscarriage (pregnancy loss prior to 20 weeks gestation) and ectopic pregnancy. We used electronic health records of all female residents in Scotland who were vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Primary analyses used unvaccinated women from the pre-pandemic period as controls (historical controls) matched (3:1) on maternal age, gestational age at vaccination, and season of conception; with adjustment for maternal deprivation level, rural/urban status and clinical vulnerability. Supplementary analyses used unvaccinated women from the pandemic period as controls (contemporary controls). Analyses of outcomes following SARS-CoV-2 infection were undertaken with infection rather than vaccination as the exposure. Following COVID-19 vaccination, the rate of miscarriage was 9.1% (n = 1,716) and ectopic pregnancy 1.2% (n = 126). Primary analyses found no association between vaccination and miscarriage (adjusted Odds Ratio [aOR] = 1.02, 95% Confidence Interval [CI] = 0.96–1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92–1.38). Primary analyses also found no association between SARS-CoV-2 infection and miscarriage or ectopic pregnancy. Results of supplementary analyses were similar to primary analyses. Given that SARS-CoV-2 infection in later pregnancy carries substantial risks to women and babies, our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.",,doi:https://doi.org/10.21203/rs.3.rs-1955486/v1; html:https://europepmc.org/article/PPR/PPR534199; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR534199&type=FILE&fileName=EMS153081-pdf.pdf&mimeType=application/pdf; pdf:https://www.nature.com/articles/s41467-022-33937-y.pdf PPR600925,https://doi.org/10.1101/2023.01.20.23284849,Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform,"Zheng B, Tazare J, Nab L, Mehrkar A, MacKenna B, Goldacre B, Douglas IJ, Tomlinson LA.",,No Journal Info,2023,2023-01-22,Y,,,,"

Objective

To compare the effectiveness of Paxlovid vs. sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients.

Design

With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform.

Setting

Patient-level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death within the OpenSAFELY-TPP platform, covering a period where both Paxlovid and sotrovimab were first-line treatment options in community settings.

Participants

Non-hospitalised adult COVID-19 patients at high risk of severe outcomes treated with Paxlovid, sotrovimab or molnupiravir between February 11, 2022 and October 1, 2022.

Interventions

Paxlovid, sotrovimab or molnupiravir administered in the community by COVID-19 Medicine Delivery Units.

Main outcome measure

COVID-19 related hospitalisation or COVID-19 related death within 28 days after treatment initiation.

Results

A total of 7683 eligible patients treated with Paxlovid (n=4836) and sotrovimab (n=2847) were included in the main analysis. The mean age was 54.3 (SD=14.9) years; 64% were female, 93% White and 93% had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 52 (0.68%) COVID-19 related hospitalisations/deaths were observed (33 (0.68%) treated with Paxlovid and 19 (0.67%) with sotrovimab). Cox proportional hazards model stratified by region showed that after adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, treatment with Paxlovid was associated with a similar risk of outcome event as treatment with sotrovimab (HR=1.14, 95% CI: 0.62 to 2.08; P=0.673). Results from propensity score weighted Cox model also showed comparable risks in these two treatment groups (HR=0.88, 95% CI: 0.45 to 1.71; P=0.700). An exploratory analysis comparing Paxlovid users with 802 molnupiravir users (11 (1.37%) COVID-19 related hospitalisations/deaths) showed some evidence in favour of Paxlovid but with variation in the effect estimates between models (HR ranging from 0.26 to 0.61).

Conclusion

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received Paxlovid and sotrovimab between February and October 2022, when different subvariants of Omicron were dominant.",,doi:https://doi.org/10.1101/2023.01.20.23284849; html:https://europepmc.org/article/PPR/PPR600925; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR600925&type=FILE&fileName=EMS163205-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/22/2023.01.20.23284849.full.pdf PPR542738,https://doi.org/10.1101/2022.09.09.22279759,Nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination,"Liew F, Talwar S, Cross A, Willett BJ, Scott S, Logan N, Siggins MK, Swieboda D, Sidhu JK, Efstathiou C, Moore SC, Davis C, Mohamed N, Nunag J, King C, Roger Thompson AA, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho L, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton DG, Dunachie S, Quint JK, Evans RA, Wain LV, Fontanella S, de Silva TI, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites RS, Turtle L, Openshaw PJ.",,No Journal Info,2022,2022-09-09,Y,,,,"

Summary

Background

Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods

Plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.

Findings

Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months. Nasal and plasma anti-S IgG remained elevated for at least 12 months with high plasma neutralising titres against all variants. Of 180 with complete data, 160 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal. Samples 12 months after admission showed no association between nasal IgA and plasma IgG responses, indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.

Interpretation

The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

Research in context

Evidence before the study

While systemic immunity to SARS-CoV-2 is important in preventing severe disease, mucosal immunity prevents viral replication at the point of entry and reduces onward transmission. We searched PubMed with search terms “mucosal”, “nasal”, “antibody”, “IgA”, “COVID-19”, “SARS-CoV-2”, “convalescent” and “vaccination” for studies published in English before 20 th July 2022, identifying three previous studies examining the durability of nasal responses that generally show nasal antibody to persist for 3 to 9 months. However, these studies were small or included individuals with mild COVID-19. One study of 107 care-home residents demonstrated increased salivary IgG (but not IgA) after two doses of mRNA vaccine, and another examined nasal antibody responses after infection and subsequent vaccination in 20 cases, demonstrating rises in both nasal IgA and IgG 7 to 10 days after vaccination.

Added value of this study

Studying 446 people hospitalised for COVID-19, we show durable nasal and plasma IgG responses to ancestral (B.1 lineage) SARS-CoV-2, Delta and Omicron (BA.1) variants up to 12 months after infection. Nasal antibody induced by infection with pre-Omicron variants, bind Omicron virus in vitro better than plasma antibody. Although nasal and plasma IgG responses were enhanced by vaccination, Omicron binding responses did not reach levels equivalent to responses for ancestral SARS-CoV-2. Using paired plasma and nasal samples collected approximately 12 months after infection, we show that nasal IgA declines and shows a minimal response to vaccination whilst plasma antibody responses to S antigen are well maintained and boosted by vaccination.

Implications of all the available evidence

After COVID-19 and subsequent vaccination, Omicron binding plasma and nasal antibody responses are only moderately enhanced, supporting the need for booster vaccinations to maintain immunity against SARS-CoV-2 variants. Notably, there is distinct compartmentalisation between nasal IgA and plasma IgA and IgG responses after vaccination. These findings highlight the need for vaccines that induce robust and durable mucosal immunity.",,doi:https://doi.org/10.1101/2022.09.09.22279759; html:https://europepmc.org/article/PPR/PPR542738; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR542738&type=FILE&fileName=EMS154137-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/09/2022.09.09.22279759.full.pdf @@ -74,8 +74,8 @@ PPR584146,https://doi.org/10.1101/2022.12.12.22283200,"COVID-19 Vaccination in P PPR532697,https://doi.org/10.1101/2022.08.13.22278733,QCovid 4 - Predicting risk of death or hospitalisation from COVID-19 in adults testing positive for SARS-CoV-2 infection during the Omicron wave in England,"Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CA.",,No Journal Info,2022,2022-08-16,Y,,,,"

ABSTRACT

Objectives

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

Design

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

Settings and study period

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

Main outcome measures

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

Results

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

Conclusion

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

What is known

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

What this study adds

The QCOVID4 risk algorithm using data from the Omicron wave now includes number of vaccination doses and prior SARS-CoV-2 infection. It has excellent performance both for ranking individuals (discrimination) and predicting levels of absolute risk (calibration) and can be used for targeting COVID-19 vaccination and therapeutics as well as individualised risk assessment. QCOVID4 more accurately identifies individuals at highest levels of absolute risk for targeted interventions than the ‘conditions-based’ approach adopted by NHS Digital based on relative risk of a list of medical conditions. Although large disparities in risks of severe COVID-19 outcomes among ethnic minority groups were observed during the early waves of the pandemic, these are much reduced now with no increased risk of mortality by ethnic group.",,doi:https://doi.org/10.1101/2022.08.13.22278733; html:https://europepmc.org/article/PPR/PPR532697; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR532697&type=FILE&fileName=EMS152911-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/08/16/2022.08.13.22278733.full.pdf PPR432994,https://doi.org/10.1101/2021.12.14.21267806,"REACT-1 round 15 final report: Increased breakthrough SARS-CoV-2 infections among adults who had received two doses of vaccine, but booster doses and first doses in children are providing important protection","Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,No Journal Info,2021,2021-12-16,Y,,,,"

Background

It has been nearly a year since the first vaccinations against SARS-CoV-2 were delivered in England. The third wave of COVID-19 in England began in May 2021 as the Delta variant began to outcompete and largely replace other strains. The REal-time Assessment of Community Transmission-1 (REACT-1) series of community surveys for SARS-CoV-2 infection has provided insights into transmission dynamics since May 2020. Round 15 of the REACT-1 study was carried out from 19 October to 5 November 2021.

Methods

We estimated prevalence of SARS-CoV2 infection and used multiple logistic regression to analyse associations between SARS-CoV-2 infection in England and demographic and other risk factors, based on RT-PCR results from self-administered throat and nose swabs in over 100,000 participants. We estimated (single-dose) vaccine effectiveness among children aged 12 to 17 years, and among adults compared swab-positivity in people who had received a third (booster) dose with those who had received two vaccine doses. We used splines to analyse time trends in swab-positivity.

Results

During mid-October to early-November 2021, weighted prevalence was 1.57% (1.48%, 1.66%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). Weighted prevalence increased between rounds 14 and 15 across most age groups (including older ages, 65 years and over) and regions, with average reproduction number across rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from a maximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalence at ages 17 years and below and 18 to 54 years. School-aged children had the highest weighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and 5.21% (4.61%, 5.87%) in those aged 13 to 17 years. In multiple logistic regression, age, sex, key worker status and presence of one or more children in the home were associated with swab positivity. There was evidence of heterogeneity between rounds in swab positivity rates among vaccinated individuals at ages 18 to 64 years, and differences in key demographic and other variables between vaccinated and unvaccinated adults at these ages. Vaccine effectiveness against infection in children was estimated to be 56.2% (41.3%, 67.4%) in rounds 13, 14 and 15 combined, adjusted for demographic factors, with a similar estimate obtained for round 15 only. Among adults we found that those who received a third dose of vaccine were less likely to test positive compared to those who received only two vaccine doses, with adjusted odds ratio (OR) =0.38 (0.26, 0.55).

Discussion

Swab-positivity was very high at the start of round 15, reaching a maximum around 20 to 21 October 2021, and then falling through late October with an uncertain trend in the last few days of data collection. The observational nature of survey data and the relatively small proportion of unvaccinated adults call into question the comparability of vaccinated and unvaccinated groups at this relatively late stage in the vaccination programme. However, third vaccine doses for eligible adults and the vaccination of children aged 12 years and over are associated with lower infection risk and, thus, remain a high priority (with possible extension to children aged 5-12 years). These should help reduce SARS-CoV-2 transmission during the winter period when healthcare demands typically rise.",,doi:https://doi.org/10.1101/2021.12.14.21267806; html:https://europepmc.org/article/PPR/PPR432994; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR432994&type=FILE&fileName=EMS141765-pdf.pdf&mimeType=application/pdf PPR355981,https://doi.org/10.1101/2021.06.08.21258533,The impact of co-circulating pathogens on SARS-CoV-2/COVID-19 surveillance: How concurrent epidemics may decrease true SARS-CoV-2 percent positivity,"Kovacevic A, Eggo RM, Baguelin M, de Cellès MD, Opatowski L.",,No Journal Info,2021,2021-06-12,Y,,,,"

Background

Circulation of non-SARS-CoV-2 respiratory viruses during the COVID-19 pandemic may alter quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. Here, we assess the impact of an increased circulation of other respiratory viruses on the monitoring of positivity rates of SARS-CoV-2 and interpretation of surveillance data.

Methods

Using a multi-pathogen Susceptible-Exposed-Infectious-Recovered (SEIR) transmission model formalizing co-circulation of SARS-CoV-2 and another respiratory we assess how an outbreak of secondary virus may inflate the number of SARS-CoV-2 tests and affect the interpretation of COVID-19 surveillance data. Using simulation, we assess to what extent the use of multiplex PCR tests on a subsample of symptomatic individuals can support correction of the observed SARS-CoV-2 percent positive during other virus outbreaks and improve surveillance quality.

Results

Model simulations demonstrated that a non-SARS-CoV-2 epidemic creates an artificial decrease in the observed percent positivity of SARS-CoV-2, with stronger effect during the growth phase, until the peak is reached. We estimate that performing one multiplex test for every 1,000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percent positive.

Conclusions

This study highlights that co-circulating respiratory viruses can disrupt SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex PCR, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.

Summary

COVID-19 surveillance indicators may be impacted by increased co-circulation of other respiratory viruses delaying control measure implementation. Continued surveillance through multiplex PCR testing in a subsample of the symptomatic population may play a role in fixing this problem.",,doi:https://doi.org/10.1101/2021.06.08.21258533; html:https://europepmc.org/article/PPR/PPR355981; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR355981&type=FILE&fileName=EMS127681-pdf.pdf&mimeType=application/pdf -PPR506599,https://doi.org/10.1101/2022.06.15.22276423,How acceptable is rapid whole genome sequencing for infectious disease management in hospitals? Perspectives of those involved in managing nosocomial SARS-CoV-2,"Flowers P, McLeod J, Mapp F, Stirrup O, Blackstone J, Snell LB, Peters C, Thomson E, Holmes A, Price J, Partridge D, Shallcross L, de Silva TI, Breuer J.",,No Journal Info,2022,2022-06-16,Y,,,,"

Structured summary

Background

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

Method

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

Findings

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

Conclusion

Our qualitative analysis, drawn from five diverse hospitals, shows the broad acceptability of rapid sequencing and its potential. Participants believed it could and should become an everyday technology capable of being embedded within typical hospital processes and systems. However, its future integration into existing healthcare systems will not be without challenges (e.g., resource, multi-level change) warranting further mixed methods research.",,doi:https://doi.org/10.1101/2022.06.15.22276423; html:https://europepmc.org/article/PPR/PPR506599; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR506599&type=FILE&fileName=EMS146081-pdf.pdf&mimeType=application/pdf PPR467856,https://doi.org/10.1101/2022.03.10.22272177,The Omicron SARS-CoV-2 epidemic in England during February 2022,"Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters CE, Atchinson C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,No Journal Info,2022,2022-03-13,Y,,,,"

Background:

The third wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron variant. However, rates of hospitalisations and deaths were substantially lower than in the first and second waves Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).

Findings:

We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round reproduction number (R) overall of 0.94 (0.91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,195 positive samples with sublineages determined, only one (0.1% [0.0-0.5]) corresponded to AY.39 Delta sublineage and the remainder were Omicron: N=390, 32.7% (30.0-35.4) were BA.1; N=473, 39.6% (36.8-42.5) were BA.1.1; and N=331, 27.7% (25.2-30.4) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36-0.43). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required. Funding: Department of Health and Social Care, England.",,doi:https://doi.org/10.1101/2022.03.10.22272177; html:https://europepmc.org/article/PPR/PPR467856; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR467856&type=FILE&fileName=EMS148965-pdf.pdf&mimeType=application/pdf +PPR506599,https://doi.org/10.1101/2022.06.15.22276423,How acceptable is rapid whole genome sequencing for infectious disease management in hospitals? Perspectives of those involved in managing nosocomial SARS-CoV-2,"Flowers P, McLeod J, Mapp F, Stirrup O, Blackstone J, Snell LB, Peters C, Thomson E, Holmes A, Price J, Partridge D, Shallcross L, de Silva TI, Breuer J.",,No Journal Info,2022,2022-06-16,Y,,,,"

Structured summary

Background

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

Method

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

Findings

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

Conclusion

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

Summary

Background

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

Methods

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

Findings

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

Interpretation

The rate at which estimated vaccine effectiveness waned was strikingly consistent for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test, and similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the Omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination doses.",,doi:https://doi.org/10.1101/2022.03.23.22272804; html:https://europepmc.org/article/PPR/PPR471516; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR471516&type=FILE&fileName=EMS149099-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/03/23/2022.03.23.22272804.full.pdf PPR602604,https://doi.org/10.2139/ssrn.4244745,The Effect of the COVID-19 Pandemic on the Treated Incidence of Psychotic Disorders in South London,"Spinazzola E, Meyer Z, Gray Z, Azlan A, Wratten C, Rayat M, Hiscott L, Kyriacou L, Cottrell D, Pritchard M, Quattrone A, Stewart R, Forti MD, Murray R, Quattrone D.",,No Journal Info,2022,2022-11-08,N,,,,"Background: The impact of the COVID-19 pandemic on the incidence of psychotic disorders has not yet been investigated. We, therefore, carried out an incidence study to ascertain rates of first-episode psychosis (FEP) before and during the COVID-19 pandemic in South London.

Methods: We screened the clinical records of all individuals living in the London boroughs of Southwark and Lambeth who were referred to the early intervention in psychosis services before (from 1 March 2019 to 28 February 2020) and during (from 1 March 2020 to 28 February 2021) the COVID-19 pandemic. We used Office for National Statistics (ONS) data to estimate the risk populations stratified by sex and age group. We computed crude and sex-age standardised FEP incidence per 100,000 persons-year. We used Poisson regression to calculate the incidence rate ratio (IRR) before and during the COVID-19 pandemic and to examine the incidence variation by sociodemographic factors.

Findings: A total of 321 incident cases of FEP were identified during the COVID-19 pandemic accounting for a crude rate of 70·1 (95% CI 62·39 - 77·73) per 100,000 person-year. The crude rate for the year before was 47·5 (95% CI 41·25 - 53·81). The incidence variation between the two years accounted for an adjusted IRR of 1·46 (95% CI 1·23 – 1·76).

Interpretation: The pandemic resulted in a 46% spike in the rates of first-episode psychosis. This finding should inform public health research and demonstrates the need for adequate resources for mental health secondary services.

Funding: DQ is supported by MRC/UKRI CARP (MRC CARP grant MR/W030608/1). ES and MDF are supported by MRC SRF Fellowship to MDF (MRC MR/T007818/1). RMM and RS are supported by NIHR BRC at SLaM and KCL. RS is further supported by NIHR ARC South London and DATAMIND HDR UK Mental Health Data Hub (MRC grant MR/W014386).

Declaration of Interest: None to declare.

Ethical Approval: CRIS is an anonymised system for analysing patient data, which was granted ethical approval by the Oxfordshire Research Ethics Committee (reference 08/H0606/71). All information accessed and analysed in CRIS is regularly monitored and audited. Ethical approval for this study was granted by the CRIS Oversight Committee (reference 20-061 to DQ).",,doi:https://doi.org/10.2139/ssrn.4244745; html:https://europepmc.org/article/PPR/PPR602604; doi:https://doi.org/10.2139/ssrn.4244745 PPR501055,https://doi.org/10.21203/rs.3.rs-1656915/v1,"Long-COVID in Scotland Study: a nationwide, population cohort study","Pell J, Hastie C, Lowe D, McAuley A, Winter A, Mills N, Black C, Scott J, O'Donnell C, Blane D, Browne S, Ibbotson T.",,No Journal Info,2022,2022-05-24,Y,,,,"BACKGROUNDWith increasing numbers of people infected with SARS-CoV-2, a better understanding of long-COVID is required to inform health and social care support.METHODSA nationwide, ambidirectional, population cohort was constructed of adults in Scotland with a positive SARS-CoV-2 PCR test from April 2020 to May 2021 and a matched, never infected comparison group. Recovery status, symptoms, quality of life, impaired daily activities, hospitalization and death were ascertained via repeated self-completed questionnaires, at 6, 12 and 18-months follow-up, and linkage to hospitalization and death records.RESULTSThe cohort comprised 31,486 symptomatic and 1,795 asymptomatic infected individuals, and 62,957 never infected individuals. Of the former, 1,856 (6%) had not recovered and 13,350 (42%) only partially. Lack of recovery was associated with severe (hospitalized) infection, older age, female sex, deprivation, respiratory disease, depression and multimorbidity. Twenty-four persistent symptoms were independently associated with previous infection including breathlessness (OR 3.44, 95% CI 3.29–3.59), palpitations (OR 2.51, OR 2.37–2.67), chest pain (OR 2.10, 95% CI 1.97–2.24), and confusion (OR 2.93, 95% CI 2.78–3.08). Pre-infection vaccination was associated with reduced risk of seven symptoms. Previous symptomatic infection was also associated with poorer quality of life (EQ-5D median 75 vs 80, p < 0.001) and impairment across all daily activities. Asymptomatic infection was not associated with adverse outcomes.CONCLUSIONSThe sequelae of SARS-CoV-2 infection are wide-ranging and not explained by confounding. The risk of long-COVID is greater following severe infections requiring hospitalization and absent following asymptomatic infection, whilst pre-infection vaccination may be protective.",,doi:https://doi.org/10.21203/rs.3.rs-1656915/v1; html:https://europepmc.org/article/PPR/PPR501055; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR501055&type=FILE&fileName=EMS145691-pdf.pdf&mimeType=application/pdf @@ -133,21 +133,21 @@ PPR303187,https://doi.org/10.1101/2021.03.26.21254390,Regional performance varia PPR225505,https://doi.org/10.1101/2020.10.12.20211342,Network Graph Representation of COVID-19 Scientific Publications to Aid Knowledge Discovery,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,No Journal Info,2020,2020-10-14,N,,,,"

Introduction

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

Methods

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

Results

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

Conclusion

Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity interrelationships to improve understanding of diseases such as COVID-19.",,doi:https://doi.org/10.1101/2020.10.12.20211342; html:https://europepmc.org/article/PPR/PPR225505; doi:https://doi.org/10.1101/2020.10.12.20211342 PPR468085,https://doi.org/10.1101/2022.03.11.22272276,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT1262b2 and after booster vaccination with BNT1262b2 or mRNA-1273: a population-based cohort study (COVIDENCE UK),"Vivaldi G, Jolliffe DA, Holt H, Tydeman F, Talaei M, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,No Journal Info,2022,2022-03-13,Y,,,,"

Background

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

Methods

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

Findings

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

Conclusions

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

Our findings add to growing evidence that risk factors for SARS-CoV-2 infection after primary or booster vaccinations can differ to those in unvaccinated populations, with effects attenuated for previously observed risk factors such as body-mass index and Asian ethnicity. The clear difference we observed between the efficacies of ChAdOx1 and BNT162b2 as the primary course of vaccination appears to have been reduced by the use of BNT162b2 boosters, but not by mNRA-1273 boosters. As more countries introduce booster vaccinations, future population-based studies with longer follow-up will be needed to investigate our findings further.",,doi:https://doi.org/10.1101/2022.03.11.22272276; html:https://europepmc.org/article/PPR/PPR468085; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR468085&type=FILE&fileName=EMS148998-pdf.pdf&mimeType=application/pdf; pdf:https://pureadmin.qub.ac.uk/ws/files/383171042/1_s2.0_S2666776222001971_main.pdf PPR520994,https://doi.org/10.21203/rs.3.rs-1831644/v1,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Akbari A, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-07-20,Y,,,,"

Background:

Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant women’s views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort). Methods This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. Codebook thematic analysis was used to generate themes from an open-ended question on the survey. Results Population-level data linkage (objective 1) Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (< 30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR = 0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR = 1.12, 95% CI 1.00 to 1.25) and (HR = 1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2) 69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine included protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. Conclusion Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,doi:https://doi.org/10.21203/rs.3.rs-1831644/v1; html:https://europepmc.org/article/PPR/PPR520994; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR520994&type=FILE&fileName=EMS151343-pdf.pdf&mimeType=application/pdf -PPR408448,https://doi.org/10.1101/2021.10.13.21264937,Comparative effectiveness of ChAdOx1 versus BNT162b2 COVID-19 vaccines in Health and Social Care workers in England: a cohort study using OpenSAFELY,"Hulme WJ, Williamson EJ, Green A, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson L, Palmer T, Horne E, MacKenna B, Morton CE, Mehrkar A, Fisher L, Bacon S, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AY, Mathur R, Wing K, Forbes H, Grint D, Douglas IJ, Evans SJ, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JA, Hernán M, Goldacre B.",,No Journal Info,2021,2021-10-18,Y,,,,"

Objectives

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

Design

Cohort study, emulating a comparative effectiveness trial.

Setting

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

Participants

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

Interventions

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

Main outcome measures

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

Results

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

Conclusions

In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.",,doi:https://doi.org/10.1101/2021.10.13.21264937; html:https://europepmc.org/article/PPR/PPR408448; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR408448&type=FILE&fileName=EMS137186-pdf.pdf&mimeType=application/pdf; pdf:https://research-information.bris.ac.uk/ws/files/345986511/bmj_2021_068946.full.pdf PPR160431,https://doi.org/10.1101/2020.05.05.20092296,Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area,"Sapey E, Gallier S, Mainey C, Nightingale P, McNulty D, Crothers H, Evison F, Reeves K, Pagano D, Denniston A, Nirantharakumar K, Diggle P, Ball S.",,No Journal Info,2020,2020-05-09,N,,,,"

Background

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

Methods

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

Results

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

Conclusions

Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes, further studies need to establish the underlying mechanistic pathways.","The objective of this study was to determine if specific ethnic groups are at higher risk of dying from covid-19 infection. They found that those of South Asian ethnicity may be at risk of worse COVID-19 outcomes. However, further studies are required to understand this better.",doi:https://doi.org/10.1101/2020.05.05.20092296; html:https://europepmc.org/article/PPR/PPR160431; doi:https://doi.org/10.1101/2020.05.05.20092296; pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000644.full.pdf +PPR408448,https://doi.org/10.1101/2021.10.13.21264937,Comparative effectiveness of ChAdOx1 versus BNT162b2 COVID-19 vaccines in Health and Social Care workers in England: a cohort study using OpenSAFELY,"Hulme WJ, Williamson EJ, Green A, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson L, Palmer T, Horne E, MacKenna B, Morton CE, Mehrkar A, Fisher L, Bacon S, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AY, Mathur R, Wing K, Forbes H, Grint D, Douglas IJ, Evans SJ, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JA, Hernán M, Goldacre B.",,No Journal Info,2021,2021-10-18,Y,,,,"

Objectives

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

Design

Cohort study, emulating a comparative effectiveness trial.

Setting

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

Participants

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

Interventions

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

Main outcome measures

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

Results

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

Conclusions

In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.",,doi:https://doi.org/10.1101/2021.10.13.21264937; html:https://europepmc.org/article/PPR/PPR408448; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR408448&type=FILE&fileName=EMS137186-pdf.pdf&mimeType=application/pdf; pdf:https://research-information.bris.ac.uk/ws/files/345986511/bmj_2021_068946.full.pdf PPR445654,https://doi.org/10.1101/2022.01.21.22269605,Outcomes of SARS-CoV-2 Omicron infection in residents of Long-Term Care,"Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, The COVID-19 Genomics UK (COG-UK) consortium.",,No Journal Info,2022,2022-01-23,Y,,,,"

Background

Recently there has been a rapid, global increase in SARS-CoV-2 infections associated with the Omicron variant (B.1.1.529). Although severity of Omicron cases may be reduced, the scale of infection suggests hospital admissions and deaths may be substantial. Definitive conclusions about disease severity require evidence from populations with the greatest risk of severe outcomes, such as residents of Long-Term Care Facilities (LTCFs).

Methods

We used a cohort study to compare the risk of hospital admission or death in LTCF residents in England who had tested positive for SARS-CoV-2 in the period shortly before Omicron emerged (Delta dominant) and the Omicron-dominant period, adjusting for age, sex, vaccine type, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset.

Results

Risk of hospital admission was markedly lower in 1241 residents infected in the Omicron-period (4.01% hospitalised, 95% CI: 2.87-5.59) compared to 398 residents infected in the pre-Omicron period (10.8% hospitalised, 95% CI: 8.13-14.29, adjusted Hazard Ratio 0.50, 95% CI: 0.29-0.87, p=0.014); findings were similar in residents with confirmed variant. No residents with previous infection were hospitalised in either period. Mortality was lower in the Omicron versus the pre-Omicron period, (p<0.0001).

Conclusions

Risk of severe outcomes in LTCF residents with the SARS-CoV-2 Omicron variant was substantially lower than that seen for previous variants. This suggests the current wave of Omicron infections is unlikely to lead to a major surge in severe disease in LTCF populations with high levels of vaccine coverage and/or natural immunity.

Trial Registration Number

ISRCTN 14447421",,doi:https://doi.org/10.1101/2022.01.21.22269605; html:https://europepmc.org/article/PPR/PPR445654; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR445654&type=FILE&fileName=EMS142621-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/27/2022.01.21.22269605.full.pdf PPR496296,https://doi.org/10.1101/2022.05.09.22274769,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-05-11,N,,,,"

Background

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

Objectives

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

Design

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

Setting and participants

Objective:

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

Outcomes

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

Results

Population-level data linkage (objective 1)

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

Survey responses (objective 2)

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

Conclusion

Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,doi:https://doi.org/10.1101/2022.05.09.22274769; html:https://europepmc.org/article/PPR/PPR496296; doi:https://doi.org/10.1101/2022.05.09.22274769 PPR382446,https://doi.org/10.1101/2021.08.12.21261987,Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2,"Eales O, Walters CE, Wang H, Haw D, Ainslie KEC, Atchison C, Page AJ, Prosolek SJ, Trotter AJ, Le Viet T, Alikhan N, Jackson LM, Ludden C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-08-13,Y,,,,"

Background

Community surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administered throat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community.

Methods

During round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines.

Results

We estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportion of positive individuals detected on first swab, P 0 , was found to be higher for those with an initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in social distancing measures.

Discussion

Home self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has high overall sensitivity. However, participants’ time-since-infection, symptom status and viral lineage affect the probability of detection and the duration of positivity. These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data, and provide a reliable means to obtain community infection estimates to inform policy response.",,doi:https://doi.org/10.1101/2021.08.12.21261987; html:https://europepmc.org/article/PPR/PPR382446; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR382446&type=FILE&fileName=EMS132863-pdf.pdf&mimeType=application/pdf -PPR365249,https://doi.org/10.1101/2021.06.28.21259452,"Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,No Journal Info,2021,2021-07-03,Y,,,,"

Summary

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of available evidence

There is a high prevalence of persistent symptoms beyond 12 weeks after acute COVID-19, with little evidence of decline thereafter. This highlights the needs for greater support for patients, both through specialised services and, for those from low-income settings, financial support. The understanding that there are distinct clusters of persistent symptoms, the most common of which is dominated by fatigue, is important for the recognition and clinical management of the condition outside of specialised services.",,doi:https://doi.org/10.1101/2021.06.28.21259452; html:https://europepmc.org/article/PPR/PPR365249; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR365249&type=FILE&fileName=EMS129876-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/03/2021.06.28.21259452.full.pdf PPR373640,https://doi.org/10.1101/2021.07.21.21260926,"Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults","Ward H, Atchison C, Whitaker M, Donnelly CA, Riley S, Ashby D, Darzi A, Barclay WS, Cooke G, Elliott P, for the REACT study team.",,No Journal Info,2021,2021-07-22,Y,,,,"

Background

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

Methods

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

Results

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

Interpretation

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

Summary

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of available evidence

There is a high prevalence of persistent symptoms beyond 12 weeks after acute COVID-19, with little evidence of decline thereafter. This highlights the needs for greater support for patients, both through specialised services and, for those from low-income settings, financial support. The understanding that there are distinct clusters of persistent symptoms, the most common of which is dominated by fatigue, is important for the recognition and clinical management of the condition outside of specialised services.",,doi:https://doi.org/10.1101/2021.06.28.21259452; html:https://europepmc.org/article/PPR/PPR365249; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR365249&type=FILE&fileName=EMS129876-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/03/2021.06.28.21259452.full.pdf PPR339757,https://doi.org/10.1101/2021.05.08.21256867,SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples,"Eales O, Page AJ, Tang SN, Walters CE, Wang H, Haw D, Trotter AJ, Viet TL, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly CA, O’Grady J, Volz E, Darzi A, Ward H, Elliott P, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-05-14,Y,,,,"Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.",,doi:https://doi.org/10.1101/2021.05.08.21256867; html:https://europepmc.org/article/PPR/PPR339757; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR339757&type=FILE&fileName=EMS127680-pdf.pdf&mimeType=application/pdf PPR447312,https://doi.org/10.1101/2022.01.26.22269885,SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI),"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2022,2022-01-27,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

Double-dose vaccination elicits robust and stable antibody responses in older LTCF residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,doi:https://doi.org/10.1101/2022.01.26.22269885; html:https://europepmc.org/article/PPR/PPR447312; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR447312&type=FILE&fileName=EMS142768-pdf.pdf&mimeType=application/pdf; pdf:https://discovery.ucl.ac.uk/10147322/1/spike-waning-JID.pdf PPR278785,https://doi.org/10.1101/2021.02.03.21251004,Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England,"Nafilyan V, Islam N, Mathur R, Ayoubkhani D, Banerjee A, Glickman M, Humberstone B, Diamond I, Khunti K.",,No Journal Info,2021,2021-02-05,Y,,,,"

Background

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

Methods

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

Results

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

Conclusion

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

The risk of COVID-19 mortality during the first wave of the pandemic was elevated in people from ethnic minority background. An appreciable reduction in the difference in COVID-19 mortality in the second wave of the pandemic between people from Black ethnic background and people from the White British group is reassuring, but the continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy response. Focusing on treating underlying conditions, although important, may not be enough in reducing the inequalities in COVID-19 mortality. Focused public health policy as well as community mobilisation and participatory public health campaign involving community leaders may help reduce the existing and widening inequalities in COVID-19 mortality.",,doi:https://doi.org/10.1101/2021.02.03.21251004; html:https://europepmc.org/article/PPR/PPR278785; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR278785&type=FILE&fileName=EMS116038-pdf.pdf&mimeType=application/pdf; pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00765-1.pdf PPR354056,https://doi.org/10.1101/2021.06.08.21258535,Altered neutrophil phenotype and function in non-ICU hospitalised COVID-19 patients correlated with disease severity,"Belchamber K, Thein O, Hazeldine J, Grudzinska F, Hughes M, Jasper A, Yip K, Sapey E, Parekh D, Thickett D, Scott A.",,No Journal Info,2021,2021-06-08,Y,,,,"

Rational

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

Objectives

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

Methods

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

Results

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

Conclusion

COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.",,doi:https://doi.org/10.1101/2021.06.08.21258535; html:https://europepmc.org/article/PPR/PPR354056; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR354056&type=FILE&fileName=EMS127476-pdf.pdf&mimeType=application/pdf PPR403344,https://doi.org/10.1101/2021.10.01.21264408,Reduced amplification efficiency of the RNA-dependent-RNA-polymerase (RdRp) target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests,"Valley-Omar Z, Marais G, Iranzadeh A, Naidoo M, Korsman S, Maponga T, Hussey H, Davies M, Boulle A, Doolabh D, Laubscher M, Deetlefs J, Maritz J, Scott L, Msomi N, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, Hsiao N.",,No Journal Info,2021,2021-10-01,Y,,,,"Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced PCR amplification efficiency of the RdRp gene target of the Seegene, Allplex 2019-nCoV diagnostic assay when detecting the Delta variant. We propose that this can be used as a surrogate for variant detection.",,doi:https://doi.org/10.1101/2021.10.01.21264408; html:https://europepmc.org/article/PPR/PPR403344; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR403344&type=FILE&fileName=EMS136740-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/01/2021.10.01.21264408.full.pdf PPR417361,https://doi.org/10.1101/2021.11.08.21265312,"Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 56 million people: phenotypes, severity, waves & vaccination","Thygesen JH, Tomlinson C, Hollings S, Mizani M, Handy A, Akbari A, Banerjee A, Cooper J, Lai A, Li K, Mateen B, Sattar N, Sofat R, Torralbo A, Wu H, Wood A, Sterne JAC, Pagel C, Whiteley W, Sudlow C, Hemingway H, Denaxas S.",,No Journal Info,2021,2021-11-09,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Research in Context

Evidence before the study

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

Added value of this study

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

Implications of all the available evidence

The COVID-19 phenotypes and trajectory analysis framework outlined produce a reproducible, extensible and repurposable means to generate national-scale data to support critical policy decision making. By modelling patient trajectories as a series of interactions with healthcare systems, and linking these to demographic and outcome data, we provide a means to identify and prioritise care pathways associated with adverse outcomes and highlight healthcare system ‘touch points’ which may act as tangible targets for intervention.",,doi:https://doi.org/10.1101/2021.11.08.21265312; html:https://europepmc.org/article/PPR/PPR417361; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR417361&type=FILE&fileName=EMS138265-pdf.pdf&mimeType=application/pdf -PPR401642,https://doi.org/10.1101/2021.09.27.21264166,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibody in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2021,2021-09-29,Y,,,,"

Background

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

Methods

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

Results

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

Interpretation

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

Funding

UK Government Department of Health and Social Care.

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all available research

A substantial proportion of the LTCF population will have some level of natural immunity to infection as a result of past infection. Immunological studies have highlighted greater antibody responses to vaccination in seropositive individuals, so vaccine efficacy in this population may be affected by this large pool of individuals who have survived past infection. In addition, although the presence of nucleocapsid-specific antibodies is generally considered as the standard marker for prior infection, we find that antibody waning is such that up to 50% of people will lose detectable antibody responses within eight months. Individual prior natural infection history is critical to assess the impact of factors such as vaccine response or protection against re-infection. These findings may have implications for duration of immunity following natural infection and indicate that alternative assays for prior infection should be developed.",,doi:https://doi.org/10.1101/2021.09.27.21264166; html:https://europepmc.org/article/PPR/PPR401642; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR401642&type=FILE&fileName=EMS136680-pdf.pdf&mimeType=application/pdf; pdf:http://www.thelancet.com/article/S2666756821002828/pdf PPR359256,https://doi.org/10.1101/2021.06.17.21259103,REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant,"Riley S, Wang H, Eales O, Haw D, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Prosolek SJ, Trotter AJ, Le Viet T, Alikhan N, Jackson LM, Ludden C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-06-21,Y,,,,"

Background

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

Methods

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

Results

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

Discussion

The extent to which exponential growth continues, or slows down as a consequence of the continued rapid roll-out of the vaccination programme, including to young adults, requires close monitoring. Data on community prevalence are vital to track the course of the epidemic and inform ongoing decisions about the timing of further lifting of restrictions in England.",,doi:https://doi.org/10.1101/2021.06.17.21259103; html:https://europepmc.org/article/PPR/PPR359256; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR359256&type=FILE&fileName=EMS128173-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/06/21/2021.06.17.21259103.full.pdf +PPR401642,https://doi.org/10.1101/2021.09.27.21264166,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibody in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2021,2021-09-29,Y,,,,"

Background

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

Methods

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

Results

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

Interpretation

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

Funding

UK Government Department of Health and Social Care.

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all available research

A substantial proportion of the LTCF population will have some level of natural immunity to infection as a result of past infection. Immunological studies have highlighted greater antibody responses to vaccination in seropositive individuals, so vaccine efficacy in this population may be affected by this large pool of individuals who have survived past infection. In addition, although the presence of nucleocapsid-specific antibodies is generally considered as the standard marker for prior infection, we find that antibody waning is such that up to 50% of people will lose detectable antibody responses within eight months. Individual prior natural infection history is critical to assess the impact of factors such as vaccine response or protection against re-infection. These findings may have implications for duration of immunity following natural infection and indicate that alternative assays for prior infection should be developed.",,doi:https://doi.org/10.1101/2021.09.27.21264166; html:https://europepmc.org/article/PPR/PPR401642; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR401642&type=FILE&fileName=EMS136680-pdf.pdf&mimeType=application/pdf; pdf:http://www.thelancet.com/article/S2666756821002828/pdf PPR592262,https://doi.org/10.1101/2023.01.04.23284174,Ethnic differences in the indirect impacts of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: An observational cohort study using OpenSAFELY,"Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EP, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AY, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, the longitudinal health and wellbeing collaborative and the OpenSAFELYcollaborative.",,No Journal Info,2023,2023-01-05,Y,,,,"

Background

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

Methods

We conducted a cohort study using OpenSAFELY (2018-2022). We grouped ethnicity (exposure), into five categories: White, South Asian, Black, Other, Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (e.g., blood pressure measurements) before and after 23rd March 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to: diabetes, cardiovascular disease, respiratory disease, and mental health before and after 23rd March 2020.

Findings

Of 14,930,356 adults in 2020 with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to White. There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in White ethnicity. Relatively, ethnic differences narrowed for heart failure admission in those of Asian and Black ethnicity compared to White. For other outcomes the pandemic had minimal impact on ethnic differences.

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).

Research in context

Evidence before this study

We searched MEDLINE from inception to 7th September 2022, for articles published in English, including the title/abstract search terms (healthcare disruption OR indirect impact OR miss* diagnos* OR delayed diagnos* OR service disruption) AND (sars-cov-2 OR covid-19 OR pandemic OR lockdown) AND (ethnic*). Of the seven studies identified, two broadly investigated the indirect impacts of the pandemic on non-COVID outcomes and reported ethnic differences. However, these two only included data until January 2021 at the latest. Other studies investigated just one disease area such as dementia or diabetes and frequently did not have the power to investigate specific ethnic groups.

Added value of this study

This is one of the largest studies to describe how the pandemic impacted ethnic differences in clinical monitoring at primary care and hospital admissions for non-COVID conditions (across four disease areas: cardiovascular disease, diabetes mellitus, respiratory disease and mental health) in England. A study population of nearly 15 million people, allowed the examination of five ethnic groups, and data until April 2022 allowed the evaluation of impacts for a longer period than previous studies.We showed that clinical monitoring had still not returned to pre-pandemic levels even by April 2022. Ethnic differences in clinical monitoring were seen pre-pandemic, though not in diabetes measures, these differences were either not impacted or reduced during the pandemic. We also showed that there were ethnic differences in hospital admissions, for many outcomes the pandemic did not impact these differences but there were some exceptions, in particular for diabetic ketoacidosis admissions in those of Black ethnicity and heart failure admissions for those of Black and Asian ethnicities.

Implications of all the available evidence

We found that the pandemic reduced ethnic inequalities for some outcomes (in hospitalisations for diabetic ketoacidosis and heart failure). However, these were driven by greater absolute increases in admissions for black and asian groups (diabetic ketoacidosis) and white groups (heart failure), which warrant further investigation to understand the underlying causes.",,doi:https://doi.org/10.1101/2023.01.04.23284174; html:https://europepmc.org/article/PPR/PPR592262; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR592262&type=FILE&fileName=EMS159410-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/05/2023.01.04.23284174.full.pdf PPR380903,https://doi.org/10.1101/2021.08.10.21261834,Immuno-proteomic profiling reveals abundant airway CD8 T cells and ongoing epithelial injury in prolonged post-COVID19 respiratory disease,"Vijayakumar B, Boustani K, Ogger PP, Papadaki A, Tonkin J, Orton CM, Ghai P, Suveizdyte K, Hewitt RJ, Snelgrove RJ, Molyneaux PL, Garner JL, Peters JE, Shah PL, Lloyd CM, Harker JA.",,No Journal Info,2021,2021-08-10,Y,,,,"

Summary

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

Highlights

The post-COVID19 airway is characterized by increased cytotoxic lymphocytes. Distinct airway proteomes are associated with the airway immune cell landscape. The peripheral blood does not predict immune-proteome alterations in the airway post-COVID19. Persistent abnormalities in the airway immune-proteome post-COVID19 airways correlate with ongoing epithelial damage.",,doi:https://doi.org/10.1101/2021.08.10.21261834; html:https://europepmc.org/article/PPR/PPR380903; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR380903&type=FILE&fileName=EMS132662-pdf.pdf&mimeType=application/pdf PPR230575,https://doi.org/10.1101/2020.10.26.20219725,"Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults","Ward H, Cooke G, Atchison C, Whitaker M, Elliott J, Moshe M, Brown JC, Flower B, Daunt A, Ainslie K, Ashby D, Donnelly C, Riley S, Darzi A, Barclay W, Elliott P, for the REACT study team.",,No Journal Info,2020,2020-10-27,Y,,,,"

Background

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

Methods

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

Results

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

Discussion

These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.",,doi:https://doi.org/10.1101/2020.10.26.20219725; html:https://europepmc.org/article/PPR/PPR230575; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR230575&type=FILE&fileName=EMS101563-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/27/2020.10.26.20219725.full.pdf @@ -179,8 +179,8 @@ PPR435279,https://doi.org/10.1101/2021.12.20.21268098,"Therapies for Long COVID PPR625587,https://doi.org/10.2139/ssrn.4369346,"The Impact of the COVID-19 Pandemic on Anti-Psychotic Prescribing in Individuals with Autism, Dementia, Learning Disability, Serious Mental Illness or Living in a Care Home: A Federated Analysis of 59 Million Patients’ Primary Care Records in Situ Using OpenSAFELY","Macdonald O, Green A, Walker A, Curtis H, Croker R, Brown A, Butler-Cole B, Andrews C, Massey J, Inglesby P, Morton C, Fisher L, Morley J, Mehrkar A, Bacon S, Davy S, Evans D, Dillingham I, Ward T, Hulme W, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Parkes N, Goldacre B, Mackenna B.",,No Journal Info,2023,2023-03-01,N,,,,"Background: The COVID-19 pandemic significantly affected health and social care services. We aimed to explore whether this affected antipsychotic prescribing in at-risk populations.

Methods: With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We calculated the monthly prevalence of antipsychotic prescribing in these groups, as well as the incidence of new prescriptions in each month (Jan 2019-Dec 2021).

Findings: The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95%CI 82.30-83.19) in Jan-Mar 2019 to 90.1 (95%CI 89.68-90.60) in Oct-Dec 2021 and from 154.61 (95%CI 153.79-155.43) to 166.95 (95%CI 166.23-167.67) in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the rate of prescribing per 1000 decreased from 122.97 (95%CI 122.29-123.66) to 119.29 (95%CI 118.68-119.91), and from 54.91 (95%CI 54.52-55.29) to 51.04 (95%CI 50.74-51.35) respectively.

Interpretation: During the lockdowns in 2020, we observed a significant spike in antipsychotic prescribing in the dementia and care home groups. We have shown that these peaks are likely due to prescribing of antipsychotics for palliative care. Over the study period, we observed gradual increases in antipsychotic use in dementia and care home patients and decreases in their use in patients with learning disability or autism.

Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). In addition, the OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2- 0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). BG has also received funding from: the Bennett Foundation, the Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation; all Bennett Institute staff are supported by BG’s grants on this work. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data. ID holds grants from NIHR and GSK. OM is employed by Oxford Health as Lead Learning Disabilities pharmacist and was funded by Buckinghamshire, Oxfordshire and Berkshire West Integrated Care System for this project.

Declaration of Interest: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare the following: BG has received research funding from the Laura and John Arnold Foundation, the NHS National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK (HDRUK), the Health Foundation, and the World Health Organisation; he also receives personal income from speaking and writing for lay audiences on the misuse of science. OM is a member of the College of Mental Health Pharmacy Council and has received personal funding from CMHP and Aston university for teaching and supporting training in psychiatric pharmacy.

Ethical Approval: NHS England is the data controller; EMIS and TPP are the data processors; and the key researchers on OpenSAFELY are acting on behalf of NHS England. This implementation of OpenSAFELY is hosted within the EMIS and TPP environments which are accredited to the ISO 27001 information security standard and are NHS IG Toolkit compliant;[30,31] patient data has been pseudonymised for analysis and linkage using industry standard cryptographic hashing techniques; all pseudonymised datasets transmitted for linkage onto OpenSAFELY are encrypted; access to the platform is via a virtual private network (VPN) connection, restricted to a small group of researchers; the researchers hold contracts with NHS England and only access the platform to initiate database queries and statistical models; all database activity is logged; only aggregate statistical outputs leave the platform environment following best practice for anonymisation of results such as statistical disclosure control for low cell counts.[32] The OpenSAFELY research platform adheres to the obligations of the UK General Data Protection Regulation (GDPR) and the Data Protection Act 2018. In March 2020, the Secretary of State for Health and Social Care used powers under the UK Health Service (Control of Patient Information) Regulations 2002 (COPI) to require organisations to process confidential patient information for the purposes of protecting public health, providing healthcare services to the public and monitoring and managing the COVID-19 outbreak and incidents of exposure; this sets aside the requirement for patient consent.[33] Taken together, these provide the legal bases to link patient datasets on the OpenSAFELY platform. GP practices, from which the primary care data are obtained, are required to share relevant health information to support the public health response to the pandemic, and have been informed of the OpenSAFELY analytics platform. This study was approved by the Health Research Authority (REC reference 20/LO/0651) and by the LSHTM Ethics Board (reference 21863).",,doi:https://doi.org/10.2139/ssrn.4369346; html:https://europepmc.org/article/PPR/PPR625587; doi:https://doi.org/10.2139/ssrn.4369346; doi:https://doi.org/10.1101/2023.01.05.23284214 PPR241483,https://doi.org/10.1101/2020.11.19.20234849,Community factors and excess mortality in first wave of the COVID-19 pandemic,"Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",,No Journal Info,2020,2020-11-22,Y,,,,"Risk factors for increased risk of death from Coronavirus Disease 19 (COVID-19) have been identified 1,2 but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality at the community level during the first wave of the pandemic in England. We used geocoded data on all deaths in people aged 40 years and older during March-May 2020 compared with 2015-2019 in 6,791 local communities. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or high percent of people with a non-White ethnicity (including Black, Asian and other minority ethnic groups). Conversely, after accounting for other community characteristics, we found no association between population density or air pollution and excess mortality. Overall, the social and environmental variables accounted for around 15% of the variation in mortality at community level. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed if England and other industrialised countries are to avoid further widening of inequalities in mortality patterns during the second wave.",,doi:https://doi.org/10.1101/2020.11.19.20234849; html:https://europepmc.org/article/PPR/PPR241483; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR241483&type=FILE&fileName=EMS105015-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/22/2020.11.19.20234849.full.pdf PPR357631,https://doi.org/10.1101/2021.06.11.21258690,SARS-CoV-2 is associated with changes in brain structure in UK Biobank,"Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JL, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM.",,No Journal Info,2021,2021-06-15,N,,,,"There is strong evidence for brain-related abnormalities in COVID-19 1–13 . It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51–81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.",,doi:https://doi.org/10.1101/2021.06.11.21258690; html:https://europepmc.org/article/PPR/PPR357631; doi:https://doi.org/10.1101/2021.06.11.21258690 -PPR454366,https://doi.org/,Inferring Risks of Coronavirus Transmission from Community Household Data,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Walker AS.",,No Journal Info,2021,2021-12-02,N,,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) Susceptible-Infectious Transmission Probabilities (SITPs) of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,arxiv:https://arxiv.org/abs/2104.04605v3; html:https://europepmc.org/article/PPR/PPR454366 PPR394718,https://doi.org/10.1101/2021.09.10.21263372,Localising Vaccination Services: Qualitative Insights on an Orthodox Jewish Collaboration with Public health during the UK coronavirus Vaccine Programme,"Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NR, Lal S, Eggo RM, Marks M, Chantler T.",,No Journal Info,2021,2021-09-15,Y,,,,"Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation.

Methods:

included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders’ response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.",,doi:https://doi.org/10.1101/2021.09.10.21263372; html:https://europepmc.org/article/PPR/PPR394718; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR394718&type=FILE&fileName=EMS135122-pdf.pdf&mimeType=application/pdf +PPR454366,https://doi.org/,Inferring Risks of Coronavirus Transmission from Community Household Data,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Walker AS.",,No Journal Info,2021,2021-12-02,N,,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) Susceptible-Infectious Transmission Probabilities (SITPs) of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,arxiv:https://arxiv.org/abs/2104.04605v3; html:https://europepmc.org/article/PPR/PPR454366 PPR294760,https://doi.org/10.1101/2021.03.09.21252736,"Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","The RECOVERY Collaborative Group, Horby PW, Estcourt L, Peto L, Emberson JR, Emberson JR, Staplin N, Spata E, Pessoa-Amorim G, Campbell M, Roddick A, Brunskill NE, George T, Zehnder D, Tiberi S, Aung NN, Uriel A, Widdrington J, Koshy G, Brown T, Scott S, Baillie JK, Buch MH, Chappell LC, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Mafham M, Roberts D, Haynes R, Landray MJ.",,No Journal Info,2021,2021-03-10,Y,,,,"

ABSTRACT

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant refs: MC_PC_19056; COV19-RECPLA).",,doi:https://doi.org/10.1101/2021.03.09.21252736; html:https://europepmc.org/article/PPR/PPR294760; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR294760&type=FILE&fileName=EMS119130-pdf.pdf&mimeType=application/pdf; pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/90411/7/1-s2.0-S0140673621008977-main.pdf PPR187496,https://doi.org/10.1101/2020.07.15.20151852,"Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial","Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR, Wiselka M, Ustianowski A, Elmahi E, Prudon B, Whitehouse A, Felton T, Williams J, Faccenda J, Underwood J, Baillie JK, Chappell L, Faust SN, Jaki T, Jeffery K, Lim WS, Montgomery A, Rowan K, Tarning J, Watson JA, White NJ, Juszczak E, Haynes R, Landray MJ.",,No Journal Info,2020,2020-07-15,Y,,,,"

ABSTRACT

Background

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

Methods

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

Results

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

Conclusions

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

Funding

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

Trial registrations

The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).",,doi:https://doi.org/10.1101/2020.07.15.20151852; html:https://europepmc.org/article/PPR/PPR187496; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR187496&type=FILE&fileName=EMS87168-pdf.pdf&mimeType=application/pdf; pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022926?articleTools=true PPR601867,https://doi.org/10.2139/ssrn.3970707,Predicting and Validating Risk of Pre-Pandemic and Excess Mortality in Individuals With Chronic Kidney Disease,"Dashtban M, Mizani MA, Denaxas S, Nitsch D, Quint J, Corbett R, Mamza JB, Morris T, Mamas M, Lawlor DA, Khunti K, CVD-COVID consortium, Sudlow C, Hemingway H, Banerjee A.",,No Journal Info,2021,2021-11-24,N,,,,"Background: Chronic kidney disease (CKD) is associated with increased risk of baseline mortality and severe coronavirus (COVID-19) infection, but analyses of risk across different CKD stages, multimorbidity and demographic factors in population-based data are lacking. In people with CKD, we investigated comorbidities, and 1-year pre- and post-COVID-19 mortality.

Methods: In linked primary and secondary care electronic health records (CPRD data) for 3,862,012 individuals aged ≥ 30 years registered with a practice between 1997 and 2017, we identified individuals with CKD. We analysed prevalence of common comorbidities across incident and prevalent CKD, CKD stages, ethnic groups, sex, and age, using validated, openly available phenotypes. Using our published model, we estimated 1-year mortality at baseline and during the COVID-19 pandemic at different levels of population infection rate (IR) and relative risk (RR) of mortality associated with the pandemic. We used CPRD data for model development and contemporary English population during pandemic (NHS Digital Trusted Research Environment (TRE) for England: n=54 million (CKD: 2.3 million) from 1 March 2020 until 1 March 2021) for validation.

Findings: We identified 294,381 (mean age 72.5 years; and female: 59%) and 55,691 (mean 74.8 years and female: 62%) individuals with incident and prevalent CKD, respectively. Co- and multi-morbidity were more common in prevalent than incident CKD. Among individuals with incident CKD, 64% had ≥1 other moderate- or high-risk condition for COVID-19 mortality. In incident CKD, the pre-pandemic 1-year mortality increased with age (e.g., 1.4% and 12.5% with 1 comorbidity, and <50 years and >80 years respectively), stage of CKD (e.g., 2.7% and 28.8% with 2 comorbidities, and stage 1 and stage 5 CKD, respectively) and number of underlying conditions (e.g. 0.8% and 6.4% in <50 years, and 8.1% and 20.1% in >80 years for 0 and 3+ conditions, respectively). At IR 10%, we predicted 31003 and 46505 (at RR 2 and 3) excess deaths over 1 year in individuals with CKD. Observed excess deaths, IR and RR were 46,473, 6.55 and 4.65, respectively . Our validation results indicate the potential of predicting direct impact of a pandemic using pre-pandemic, large-scale EHR data.

Interpretation: Individuals with CKD have high burden of comorbidities and multimorbidity, high risk of pre-pandemic mortality and predictable high risk of mortality during the pandemic, signalling prioritisation for treatment of underlying disease, non-pharmaceutical measures, and vaccination.

Funding Information: This study was funded by AstraZeneca UK Ltd. The British Heart Foundation Data Science Centre (grant No SP/19/3/34678, awarded to Health Data Research (HDR) UK) funded co development (with NHS Digital) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK data and connectivity component of the UK governments’ chief scientific adviser’s national core studies programme to coordinate national covid-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians.

Declaration of Interests: DN is Director of Informatics Research for the UK Kidney Association and on the steering group for two Glaxo-SmithKline-funded studies in Sub Saharan Africa, unrelated to this research. All other authors declare no competing interests.JQ has received grants from Asthma UK, AstraZeneca, British Lung Foundation, Bayer, Boehringer Ingelheim, Chiesi, GSK, IQVIA, MRC
and The Health Foundation, and personal fees for advisory board participation or speaking fees from AstraZeneca, Bayer, Boehringer Ingelheim and GlaxoSmithKline. JBM and TM are employed by AstraZeneca UK Ltd, a biopharmaceutical company. DAL has received funding from Wellcome, the European Research Council (ERC Advanced grant and a Horizon 2020 grant), US National Institute of Health, Diabetes UK, Roche Diagnostics and Medtronic Ltd for research unrelated to that presented here. KK is director of the University of Leicester Centre for Black Minority Ethnic Health, trustee of the South Asian Health Foundation, and chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE), he has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie/Menarini Group, Janssen and Napp. AB is supported by research funding from the National Institute for Health Research (NIHR), British Medical Association, AstraZeneca, and UK Research and Innovation, and Trustee of the South Asian Health Foundation. HH is a National Institute for Health Research (NIHR) Senior Investigator. FA and HH are funded by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. HH work is supported by: 1. Health Data Research UK (grant No. LOND1), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome Trust. AB and HH are part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No. 116074. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA; it is chaired, by DE Grobbee and SD Anker, partnering with 20
academic and industry partners and ESC. Other authors report no conflicts of interest.

Ethics Approval Statement: Approval for the study was granted by the Independent Scientific Advisory Committee (20_074R) of the Medicines and Healthcare products Regulatory Agency in the UK in accordance with the Declaration of Helsinki. The North East-Newcastle and North Tyneside 2
research ethics committee provided ethical approval for the CVD-COVID-UK/COVID-IMPACT research programme (REC No 20/NE/0161).",,doi:https://doi.org/10.2139/ssrn.3970707; html:https://europepmc.org/article/PPR/PPR601867; doi:https://doi.org/10.2139/ssrn.3970707 @@ -189,8 +189,8 @@ PPR593389,https://doi.org/10.1101/2023.01.05.23284214,"The impact of the COVID-1 PPR265323,https://doi.org/10.1101/2021.01.13.21249725,The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres,"Stephenson E, Reynolds G, Botting RA, Calero-Nieto FJ, Morgan M, Tuong ZK, Bach K, Sungnak W, Worlock KB, Yoshida M, Kumasaka N, Kania K, Engelbert J, Olabi B, Spegarova JS, Wilson NK, Mende N, Jardine L, Gardner LC, Goh I, Horsfall D, McGrath J, Webb S, Mather MW, Lindeboom RG, Dann E, Huang N, Polanski K, Prigmore E, Gothe F, Scott J, Payne RP, Baker KF, Hanrath AT, van der Loeff ICS, Barr AS, Sanchez-Gonzalez A, Bergamaschi L, Mescia F, Barnes JL, Kilich E, de Wilton A, Saigal A, Saleh A, Janes SM, Smith CM, Gopee N, Wilson C, Coupland P, Coxhead JM, Kiselev VY, van Dongen S, Bacardit J, King HW, Rostron AJ, Simpson AJ, Hambleton S, Laurenti E, Lyons PA, Meyer KB, Nikolic MZ, Duncan CJ, Smith K, Teichmann SA, Clatworthy MR, Marioni JC, Gottgens B, Haniffa M, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration.",,No Journal Info,2021,2021-01-15,Y,,,,"The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8 + effector:effector memory T cells, and proliferating CD4 + and CD8 + T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.",,doi:https://doi.org/10.1101/2021.01.13.21249725; html:https://europepmc.org/article/PPR/PPR265323; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR265323&type=FILE&fileName=EMS110618-pdf.pdf&mimeType=application/pdf PPR186543,https://doi.org/10.1101/2020.07.10.20150656,Diagnostic value of skin manifestation of SARS-CoV-2 infection,"Bataille V, Visconti A, Rossi N, Murray B, Bournot A, Wolf J, Wolf J, Ourselin S, Steves C, Spector T, Falchi M.",,No Journal Info,2020,2020-07-11,Y,,,,"SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collected on a subset of 336,847 eligible UK users of the COVID Symptom Study app, we observed that 8.8% of the swab positive cases (total: 2,021 subjects) reported either a body rash or an acral rash, compared to 5.4% of those with a negative swab test (total: 25,136). Together, these two skin presentations showed an odds ratio (OR) of 1.67 (95% confidence interval [CI]: 1.41-1.96) for being swab positive. Skin rashes were also predictive in the larger untested group of symptomatic app users (N=54,652), as 8.2% of those who had reported at least one classical COVID-19 symptom, i . e ., fever, persistent cough, and/or anosmia, also reported a rash. Data from an independent online survey of 11,546 respondents with a rash showed that in 17% of swab positive cases, the rash was the initial presentation. Furthermore, in 21%, the rash was the only clinical sign. Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other classical symptoms. Recognising rashes is important in identifying new and earlier COVID-19 cases.",,doi:https://doi.org/10.1101/2020.07.10.20150656; html:https://europepmc.org/article/PPR/PPR186543; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR186543&type=FILE&fileName=EMS87210-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/26/2020.07.10.20150656.full.pdf PPR179126,https://doi.org/10.1101/2020.06.22.20137216,"Proteomic blood profiling in mild, severe and critical COVID-19 patients","Patel H, Ashton NJ, Dobson RJ, Andersson L, Yilmaz A, Blennow K, Gisslen M, Zetterberg H.",,No Journal Info,2020,2020-06-23,N,,,,"The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in the majority of individuals leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. The purpose of this study is to explore the proteomic differences between mild, severe and critical COVID-19 positive patients. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins that associate with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.",,doi:https://doi.org/10.1101/2020.06.22.20137216; html:https://europepmc.org/article/PPR/PPR179126; doi:https://doi.org/10.1101/2020.06.22.20137216; pdf:https://www.nature.com/articles/s41598-021-85877-0.pdf -PPR672054,https://doi.org/10.1101/2023.06.06.23290826,"OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate","The OpenSAFELY Collaborative, Brown AD, Fisher L, Curtis HJ, Wiedemann M, Hulme WJ, Hopcroft LE, Cunningham C, Speed V, Costello RE, Galloway JB, Russell MD, Bechman K, Kurt Z, Croker R, Wood C, Walker AJ, Schaffer AL, Bacon SC, Mehrkar A, Hickman G, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-06-07,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

None.

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

DMARD monitoring rates transiently deteriorated during the COVID-19 pandemic, consistent with previous research on other monitoring tests. Deterioration coincided with the onset of lockdown measures, with performance recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between demographic, clinical and regional subgroups highlight opportunities to identify and tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups, and establish the clinical relevance of missed monitoring. Several studies have demonstrated the capability of the OpenSAFELY platform as a secure and efficient approach for analysing NHS primary care data at scale, generating meaningful insights on service delivery.",,doi:https://doi.org/10.1101/2023.06.06.23290826; html:https://europepmc.org/article/PPR/PPR672054; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR672054&type=FILE&fileName=EMS177037-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/07/2023.06.06.23290826.full.pdf PPR215745,https://doi.org/10.1101/2020.09.15.20194795,"A short report: Acute, non-COVID related medical admissions during the first wave of COVID-19: A retrospective comparison of changing patterns of disease","Riley B, Packer M, Gallier S, Sapey E, Atkin C.",,No Journal Info,2020,2020-09-18,Y,,,,"

Background

The COVID-19 pandemic was associated with social restrictions in the UK from 16 th March 2020. It was unclear if the lockdown period was associated with differences in the case-mix of non-COVID acute medical admissions compared with the previous year.

Methods

Retrospective data were collected for 1 st -30 th April 2019 and 1 st –30 th April 2020 from University Hospitals Birmingham NHS Foundation Trust, one of the largest hospitals in the UK with over 2 million patient contacts per year. The latter time period was chosen to coincide with the peak of COVID-19 cases in the West Midlands. All patients admitted under acute medicine during these time periods were included. COVID-19 was confirmed by SARS-Cov-2 swab or a probable case of COVID-19 based on World Health Organization diagnostic parameters. Non-COVID patients were those with a negative SARS-Cov-2 swab and no suspicion of COVID-19. Data was sourced from UHB’s in-house electronic health system (EHS).

Results

The total number of acute medical admissions fell comparing April 2019 (n = 2409) to April 2020 (n = 1682). As a proportion of total admissions, those aged under 45 years decreased, while those aged 46 and over did not change. The number of admissions due to psychiatric conditions and overdoses was higher in April 2020 (p < 0.001). When viewed as a proportion of admissions, alcohol-related admissions (p = 0.004), psychiatric conditions and overdoses (p< 0.001) increased in April 2020 than in April 2019. The proportion of patients who were in hospital due to falls also increased in April 2020 (p< 0.001). In the same period, the absolute number and the proportion of admissions that were due to non-specific chest pain, to musculoskeletal complaints and patients who self-discharged prior to assessment decreased (p = 0.02, p = 0.01 and p = 0.002 respectively). There were no significant differences in non-COVID-related intensive care admissions or mortality between the same months in the two years.

Conclusion

In this large, single-centre study, there was a change in hospitalised case-mix when comparing April 2019 with April 2020: an increase in conditions which potentially reflect social isolation (falls, drug and alcohol misuse and psychiatric illness) and a decrease in conditions which rarely require in-patient hospital treatment (musculoskeletal pain and non-cardiac chest pain) especially among younger adults. These results highlight two areas for further research; the impact of social isolation on health and whether younger adults could be offered alternative health services to avoid potentially unnecessary hospital assessment.",,doi:https://doi.org/10.1101/2020.09.15.20194795; html:https://europepmc.org/article/PPR/PPR215745; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR215745&type=FILE&fileName=EMS96159-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/09/18/2020.09.15.20194795.full.pdf +PPR672054,https://doi.org/10.1101/2023.06.06.23290826,"OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate","The OpenSAFELY Collaborative, Brown AD, Fisher L, Curtis HJ, Wiedemann M, Hulme WJ, Hopcroft LE, Cunningham C, Speed V, Costello RE, Galloway JB, Russell MD, Bechman K, Kurt Z, Croker R, Wood C, Walker AJ, Schaffer AL, Bacon SC, Mehrkar A, Hickman G, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-06-07,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

None.

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

DMARD monitoring rates transiently deteriorated during the COVID-19 pandemic, consistent with previous research on other monitoring tests. Deterioration coincided with the onset of lockdown measures, with performance recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between demographic, clinical and regional subgroups highlight opportunities to identify and tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups, and establish the clinical relevance of missed monitoring. Several studies have demonstrated the capability of the OpenSAFELY platform as a secure and efficient approach for analysing NHS primary care data at scale, generating meaningful insights on service delivery.",,doi:https://doi.org/10.1101/2023.06.06.23290826; html:https://europepmc.org/article/PPR/PPR672054; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR672054&type=FILE&fileName=EMS177037-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/07/2023.06.06.23290826.full.pdf PPR550426,https://doi.org/10.1101/2022.09.23.22280285,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray M.",,No Journal Info,2022,2022-09-25,Y,,,,"

SUMMARY

Background

Dimethyl fumarate (DMF) is an anti-inflammatory drug that has been proposed as a treatment for patients hospitalised with COVID-19

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. In this initial assessment of DMF, performed at 27 UK hospitals, eligible and consenting adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF 120mg twice daily for 2 days followed by 240mg twice daily for 8 days, or until discharge if sooner. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale, assessed using a proportional odds model. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 2 March 2021 and 18 November 2021, 713 patients were enrolled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients were receiving corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.85-1.46; p=0.42). There was no significant effect of DMF on any secondary outcome. As expected, DMF caused flushing and gastrointestinal symptoms, each in around 6% of patients, but no new adverse effects were identified.

Interpretation

In adults hospitalised with COVID-19, DMF was not associated with an improvement in clinical outcomes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,doi:https://doi.org/10.1101/2022.09.23.22280285; html:https://europepmc.org/article/PPR/PPR550426; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR550426&type=FILE&fileName=EMS154960-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/25/2022.09.23.22280285.full.pdf PPR199535,https://doi.org/10.1101/2020.08.11.20172643,The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories,"Liu Y, Morgenstern C, Kelly J, Lowe R, Jit M, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-08-12,Y,,,,"

Introduction

Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories.

Methods

We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission with data from January - June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number ( R t ) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in R t , levels of NPI intensity, time-varying changes in NPI effect and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs.

Results

There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced R t . Another three NPIs (workplace closure, income support and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g., restrictions on 1000+ people gathering were not effective, restrictions on <10 people gathering was). Evidence supporting the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs.

Conclusion

Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications taking into account these effects, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many although not all the actions policy-makers are taking to respond to the COVID-19 pandemic.",,doi:https://doi.org/10.1101/2020.08.11.20172643; html:https://europepmc.org/article/PPR/PPR199535; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR199535&type=FILE&fileName=EMS92611-pdf.pdf&mimeType=application/pdf; pdf:https://europepmc.org/articles/pmc7861967?pdf=render PPR438312,https://doi.org/10.1101/2021.12.28.21268461,Rapid turnaround multiplex sequencing of SARS-CoV-2: comparing tiling amplicon protocol performance,"Constantinides B, Webster H, Gentry J, Bastable J, Dunn L, Oakley S, Swann J, Sanderson N, Fowler PW, Ma G, Rodger G, Barrett L, Jeffery K, Peto TE, Stoesser N, Street T, Crook DW.",,No Journal Info,2022,2022-01-01,Y,,,,"Genome sequencing is pivotal to SARS-CoV-2 surveillance, elucidating the emergence and global dissemination of acquired genetic mutations. Amplicon sequencing has proven very effective for sequencing SARS-CoV-2, but prevalent mutations disrupting primer binding sites have necessitated the revision of sequencing protocols in order to maintain performance for emerging virus lineages. We compared the performance of Oxford Nanopore Technologies (ONT) Midnight and ARTIC tiling amplicon protocols using 196 Delta lineage SARS-CoV-2 clinical specimens, and 71 mostly Omicron lineage samples with S gene target failure (SGTF), reflecting circulating lineages in the United Kingdom during December 2021. 96-plexed nanopore sequencing was used. For Delta lineage samples, ARTIC v4 recovered the greatest proportion of ≥90% complete genomes (81.1%; 159/193), followed by Midnight (71.5%; 138/193) and ARTIC v3 (34.1%; 14/41). Midnight protocol however yielded higher average genome recovery (mean 98.8%) than ARTIC v4 (98.1%) and ARTIC v3 (75.4%), resulting in less ambiguous final consensus assemblies overall. Explaining these observations were ARTIC v4’s superior genome recovery in low viral titre/high cycle threshold (Ct) samples and inferior performance in high titre/low Ct samples, where Midnight excelled. We evaluated Omicron sequencing performance using a revised Midnight primer mix alongside prototype ARTIC v4.1 primers, head-to-head with the existing commercially available Midnight and ARTIC v4 protocols. The revised protocols both improved considerably the recovery of Omicron genomes and exhibited similar overall performance to one another. Revised Midnight protocol recovered ≥90% complete genomes for 85.9% (61/71) of Omicron samples vs. 88.7% (63/71) for ARTIC v4.1. Approximate cost per sample for Midnight (£12) is lower than ARTIC (£16) while hands-on time is considerably lower for Midnight (∼7 hours) than ARTIC protocols (∼9.5 hours).",,doi:https://doi.org/10.1101/2021.12.28.21268461; html:https://europepmc.org/article/PPR/PPR438312; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR438312&type=FILE&fileName=EMS142102-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/01/2021.12.28.21268461.full.pdf @@ -237,8 +237,8 @@ PPR182791,https://doi.org/10.1101/2020.07.01.182709,Genetic architecture of host PPR670288,https://doi.org/10.1101/2023.05.31.23290774,POST-COVID ORTHOPAEDIC ELECTIVE RESOURCE PLANNING USING SIMULATION MODELLING,"Harper A, Monks T, Wilson R, Redaniel MT, Eyles E, Jones T, Penfold C, Elliott A, Keen T, Pitt M, Blom A, Whitehouse M, Judge A.",,No Journal Info,2023,2023-06-05,Y,,,,"

ABSTRACT

Objectives

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

Methods

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

Results

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

Conclusions

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

Strengths and Limitations of this study

The simulation model provides rapid quantitative estimates to support post-COVID elective services recovery toward medium-term elective targets. Parameter combinations include changes to both resourcing and productivity. The interactive web app enables intuitive parameter changes by users while underlying source code can be adapted or re-used for similar applications. Patient attributes such as complexity are not included in the model but are reflected in variables such as length-of-stay and delayed discharge rates. Theatre schedules are simplified, incorporating the five key orthopaedic elective surgical procedures.",,doi:https://doi.org/10.1101/2023.05.31.23290774; html:https://europepmc.org/article/PPR/PPR670288; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR670288&type=FILE&fileName=EMS176961-pdf.pdf&mimeType=application/pdf PPR602096,https://doi.org/10.2139/ssrn.4260125,The Impact of the First Year of COVID-19 Vaccination Strategy in Brazil: An Ecological Study,"Aguilar S, Bastos LdSL, Maçaira P, Baiao FA, Simões P, Cerbino-Neto J, Ranzani O, Hamacher S, Bozza FA.",,No Journal Info,2022,2022-10-27,Y,,,,"Background: Countries have used different strategies to prioritize who be vaccinated first during the COVID-19 vaccination roll-out. No consensus exists about the best strategy to be adopted by low-and-middle-income countries with limited access to vaccines. Brazil adopted an age-based calendar strategy to reduce mortality and the burden over the healthcare system. The impact of this strategy on preventing deaths and years of life lost was not estimated.

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

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

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

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

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

Ethics Approval Statement: Data was publicly available, anonymized, and de-identified. Following ethically agreed principles on open data, this analysis did not require ethical approval in Brazil.",,doi:https://doi.org/10.2139/ssrn.4260125; html:https://europepmc.org/article/PPR/PPR602096; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR602096&type=FILE&fileName=EMS164205-pdf.pdf&mimeType=application/pdf PPR233926,https://doi.org/10.1101/2020.11.03.20220699,A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital,"Cooper DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O’Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Walker N, Stark H, De Angelis D, Seaman S, Bradley JR, Török ME, Goodfellow I, Baker S, the CITIID-NIHR BioResource COVID-19 Collaboration.",,No Journal Info,2020,2020-11-04,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

International efforts to reduce the risk of SARS-CoV-2 infection amongst HCWs need to be prioritised. The risk of SARS-CoV-2 infection amongst HCWs is heterogenous but also follows demonstrable patterns. Potential mechanisms to reduce the risk for staff working in areas with confirmed COVID-19 patients include improved training in hand hygiene and personal protective equipment (PPE), better access to high quality PPE, and frequent asymptomatic testing. Wider asymptomatic testing in healthcare facilities has the potential to reduce spread of SARS-CoV-2 within hospitals, thereby reducing patient and staff risk and limiting spread between hospitals and into the wider community. The increased risk of COVID-19 amongst BAME staff cannot be explained by purely occupational factors; however, the increased risk amongst minority ethnic groups identified here was stark and necessitates further evaluation.",,doi:https://doi.org/10.1101/2020.11.03.20220699; html:https://europepmc.org/article/PPR/PPR233926; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233926&type=FILE&fileName=EMS103610-pdf.pdf&mimeType=application/pdf -PPR676615,https://doi.org/10.1101/2023.06.14.23291389,"Cohort Profile: Born in Wales - a birth cohort with maternity, parental, and child data linkage for life course research in Wales, UK","Jones H, Seaborne M, Kennedy N, James M, Dredge S, Bandyopadhyay A, Battaglia A, Davies S, Brophy S.",,No Journal Info,2023,2023-06-15,Y,,,,"

Purpose

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

Participants

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

Findings to date

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

Future plans

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

Strengths and limitations of this study

Born in Wales has established a comprehensive, Wales-wide population-based database which consolidates clinical data from maternity, neonatal, child health, and education records. This national-scale database is supplemented by quantitative and qualitative results from surveys conducted by Born in Wales, providing rich insights into details that cannot be obtained through routinely collected data. The existence of this database enables further data linkage, facilitating life course research on the health and wellbeing of the Wales population. Missing data or errors in routine and administrative data may be constraint. A potential restriction of Born in Wales is the loss of data pertaining to individuals who relocate outside of Wales during pregnancy or after the child’s birth.",,doi:https://doi.org/10.1101/2023.06.14.23291389; html:https://europepmc.org/article/PPR/PPR676615; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR676615&type=FILE&fileName=EMS177701-pdf.pdf&mimeType=application/pdf PPR415629,https://doi.org/10.1101/2021.11.02.21265767,Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK),"Talaei M, Faustini S, Holt H, Jolliffe DA, Vivaldi G, Greenig M, Perdek N, Maltby S, Bigogno CM, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Richter AG, Shaheen SO, Martineau AR.",,No Journal Info,2021,2021-11-03,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

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

Funding

Barts Charity, Health Data Research UK.",,doi:https://doi.org/10.1101/2021.11.02.21265767; html:https://europepmc.org/article/PPR/PPR415629; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR415629&type=FILE&fileName=EMS138031-pdf.pdf&mimeType=application/pdf +PPR676615,https://doi.org/10.1101/2023.06.14.23291389,"Cohort Profile: Born in Wales - a birth cohort with maternity, parental, and child data linkage for life course research in Wales, UK","Jones H, Seaborne M, Kennedy N, James M, Dredge S, Bandyopadhyay A, Battaglia A, Davies S, Brophy S.",,No Journal Info,2023,2023-06-15,Y,,,,"

Purpose

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

Participants

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

Findings to date

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

Future plans

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

Strengths and limitations of this study

Born in Wales has established a comprehensive, Wales-wide population-based database which consolidates clinical data from maternity, neonatal, child health, and education records. This national-scale database is supplemented by quantitative and qualitative results from surveys conducted by Born in Wales, providing rich insights into details that cannot be obtained through routinely collected data. The existence of this database enables further data linkage, facilitating life course research on the health and wellbeing of the Wales population. Missing data or errors in routine and administrative data may be constraint. A potential restriction of Born in Wales is the loss of data pertaining to individuals who relocate outside of Wales during pregnancy or after the child’s birth.",,doi:https://doi.org/10.1101/2023.06.14.23291389; html:https://europepmc.org/article/PPR/PPR676615; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR676615&type=FILE&fileName=EMS177701-pdf.pdf&mimeType=application/pdf PPR233548,https://doi.org/10.1101/2020.11.01.20222315,Association between living with children and outcomes from COVID-19: an OpenSAFELY cohort study of 12 million adults in England,"Forbes H, Morton CE, Bacon S, McDonald HI, Minassian C, Brown JP, Rentsch CT, Mathur R, Schultze A, DeVito NJ, MacKenna B, Hulme WJ, Croker R, Walker AJ, Williamson EJ, Bates C, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Drysdale H, Wong AY, Cockburn J, McManus R, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Evans SJ, Bhaskaran K, Eggo RM, Goldacre B, Tomlinson LA.",,No Journal Info,2020,2020-11-02,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

Our results demonstrate no evidence of serious harms from COVID-19 to adults in close contact with children, compared to those living in households without children. This has implications for determining the benefit-harm balance of children attending school in the COVID-19 pandemic.",,doi:https://doi.org/10.1101/2020.11.01.20222315; html:https://europepmc.org/article/PPR/PPR233548; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233548&type=FILE&fileName=EMS103455-pdf.pdf&mimeType=application/pdf; pdf:https://www.bmj.com/content/bmj/372/bmj.n628.full.pdf PPR117001,https://doi.org/10.1101/2020.03.09.20033050,"The effect of control strategies that reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China","Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N, Jit M, Klepac P, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group.",,No Journal Info,2020,2020-03-12,Y,,,,"

BACKGROUND

In December 2019, a novel strain of SARS-CoV-2 emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures and efforts in response to the outbreak.

METHODS

We quantified the effects of control measures on population contact patterns in Wuhan, China, to assess their effects on the progression of the outbreak. We included the latest estimates of epidemic parameters from a transmission model fitted to data on local and internationally exported cases from Wuhan in the age-structured epidemic framework. Further, we looked at the age-distribution of cases. Lastly, we simulated lifting of the control measures by allowing people to return to work in a phased-in way, and looked at the effects of returning to work at different stages of the underlying outbreak.

FINDINGS

Changes in mixing patterns may have contributed to reducing the number of infections in mid-2020 by 92% (interquartile range: 66–97%). There are benefits to sustaining these measures until April in terms of reducing the height of the peak, overall epidemic size in mid-2020 and probability that a second peak may occur after return to work. However, the modelled effects of social distancing measures vary by the duration of infectiousness and the role school children play in the epidemic.

INTERPRETATION

Restrictions on activities in Wuhan, if maintained until April, would likely contribute to the reduction and delay the epidemic size and peak, respectively. However, there are some limitations to the analysis, including large uncertainties around estimates of R0 and the duration of infectiousness.

FUNDING

Bill and Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.","This study looks at the control strategies in Wuhan, China. The study utilised computer simulation techniques to undertand the effectiveness of measures taken and the likely impact of reducing these measures.",doi:https://doi.org/10.1101/2020.03.09.20033050; html:https://europepmc.org/article/PPR/PPR117001; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR117001&type=FILE&fileName=EMS89045-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.1016/s2468-2667(20)30073-6 PPR184537,https://doi.org/10.1101/2020.07.03.20145912,Ultraviolet A Radiation and COVID-19 Deaths in the USA with replication studies in England and Italy,"Cherrie M, Clemens T, Colandrea C, Feng Z, Webb DJ, Dibben C, Weller RB.",,No Journal Info,2020,2020-07-06,Y,,,,"

Objectives

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

Design

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

Setting

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

Main outcome measures

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

Data sources

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

Results

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

Conclusions

Our analysis, replicated in 3 independent national datasets, suggests ambient UVA exposure is associated with lower COVID-19 specific mortality. This effect is independent of vitamin D, as it occurred at irradiances below that likely to induce significant cutaneous vitamin D3 synthesis. Causal interpretations must be made cautiously in observational studies. Nonetheless this study suggests strategies for reduction of COVID-19 mortality.",,doi:https://doi.org/10.1101/2020.07.03.20145912; html:https://europepmc.org/article/PPR/PPR184537; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR184537&type=FILE&fileName=EMS87521-pdf.pdf&mimeType=application/pdf @@ -254,19 +254,19 @@ PPR204608,https://doi.org/10.1101/2020.08.19.20178137,Testing for coronavirus (S PPR496265,https://doi.org/10.1101/2022.05.10.22274890,Biopsychosocial response to the COVID-19 lockdown in people with major depressive disorder and multiple sclerosis,"Siddi S, Giné-Vázquez I, Bailon R, Matcham F, Lamers F, Kontaxis S, Laporta E, Garcia E, Arranz B, Dalla Costa G, Guerrero Pérez A, Zabalza A, Buron M, Comi G, Leocani L, Annas P, Hotopf M, Penninx B, Magyari M, Sørensen PS, Montalban X, Lavelle G, Ivan A, Oetzmann C, White MK, Difrancesco S, Locatelli P, Mohr D, Aguiló J, Narayan V, Folarin A, Dobson R, Dineley J, Leightley D, Cummins N, Vairavan S, Ranjan Y, Rashid Z, Rintala A, De Girolamo G, Preti A, Simblett S, Wykes T, Myin-Germeys I, Haro J, PAB members.",,No Journal Info,2022,2022-05-10,N,,,,"

ABSTRACT

Background

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

Methods

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

Results

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

Conclusions

Behavioral response to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDD and MS.",,doi:https://doi.org/10.1101/2022.05.10.22274890; html:https://europepmc.org/article/PPR/PPR496265; doi:https://doi.org/10.1101/2022.05.10.22274890; pdf:https://ddd.uab.cat/pub/artpub/2022/271957/271957.pdf PPR178487,https://doi.org/10.1101/2020.06.19.20135491,"Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis","The OpenSAFELY Collaborative, Schultze A, Walker AJ, MacKenna B, Morton CE, Bhaskaran K, Brown JP, Rentsch CT, Williamson E, Drysdale H, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson L, Mathur R, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Quint J, Smeeth L, Douglas IJ, Goldacre B.",,No Journal Info,2020,2020-06-20,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

This work was supported by the Medical Research Council MR/V015737/1.",,doi:https://doi.org/10.1101/2020.06.19.20135491; html:https://europepmc.org/article/PPR/PPR178487; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR178487&type=FILE&fileName=EMS88284-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/06/20/2020.06.19.20135491.full.pdf PPR408531,https://doi.org/10.1101/2021.10.18.21265046,Comparative assessment of methods for short-term forecasts of COVID-19 hospital admissions in England at the local level,"Meakin S, Abbott S, Bosse N, Munday J, Gruson H, Hellewell J, Sherratt K, Funk S, CMMID COVID-19 Working Group.",,No Journal Info,2021,2021-10-18,Y,,,,"

Background

Forecasting healthcare demand is essential in epidemic settings, both to inform situational awareness and facilitate resource planning. Ideally, forecasts should be robust across time and locations. During the COVID-19 pandemic in England, it is an ongoing concern that demand for hospital care for COVID-19 patients in England will exceed available resources.

Methods

We made weekly forecasts of daily COVID-19 hospital admissions for National Health Service (NHS) Trusts in England between August 2020 and April 2021 using three disease-agnostic forecasting models: a mean ensemble of autoregressive time series models, a linear regression model with 7-day-lagged local cases as a predictor, and a scaled convolution of local cases and a delay distribution. We compared their point and probabilistic accuracy to a mean-ensemble of them all, and to a simple baseline model of no change from the last day of admissions. We measured predictive performance using the Weighted Interval Score (WIS) and considered how this changed in different scenarios (the length of the predictive horizon, the date on which the forecast was made, and by location), as well as how much admissions forecasts improved when future cases were known.

Results

All models outperformed the baseline in the majority of scenarios. Forecasting accuracy varied by forecast date and location, depending on the trajectory of the outbreak, and all individual models had instances where they were the top- or bottom-ranked model. Forecasts produced by the mean-ensemble were both the most accurate and most consistently accurate forecasts amongst all the models considered. Forecasting accuracy was improved when using future observed, rather than forecast, cases, especially at longer forecast horizons.

Conclusions

Assuming no change in current admissions is rarely better than including at least a trend. Using confirmed COVID-19 cases as a predictor can improve admissions forecasts in some scenarios, but this is variable and depends on the ability to make consistently good case forecasts. However, ensemble forecasts can make forecasts that make consistently more accurate forecasts across time and locations. Given minimal requirements on data and computation, our admissions forecasting ensemble could be used to anticipate healthcare needs in future epidemic or pandemic settings.",,doi:https://doi.org/10.1101/2021.10.18.21265046; html:https://europepmc.org/article/PPR/PPR408531; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR408531&type=FILE&fileName=EMS137136-pdf.pdf&mimeType=application/pdf; pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02271-x -PPR291347,https://doi.org/10.21203/rs.3.rs-279400/v1,Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS,"Prieto-Alhambra D, Kostka K, Duarte-Salles T, Prats-Uribe A, Sena A, Pistillo A, Khalid S, Lai L, Golozar A, Alshammari TM, Dawoud D, Nyberg F, Wilcox A, Andryc A, Williams A, Ostropolets A, Areia C, Jung CY, Harle C, Reich C, Blacketer C, Morales D, Dorr DA, Burn E, Roel E, Tan EH, Minty E, DeFalco F, de Maeztu G, Lipori G, Alghoul H, Zhu H, Thomas J, Bian J, Park J, Roldán JM, Posada J, Banda JM, Horcajada JP, Kohler J, Shah K, Natarajan K, Lynch K, Liu L, Schilling L, Recalde M, Spotnitz M, Gong M, Matheny M, Valveny N, Weiskopf N, Shah N, Alser O, Casajust P, Park RW, Schuff R, Seager S, DuVall S, You SC, Song S, Fernández-Bertolín S, Fortin S, Magoc T, Falconer T, Subbian V, Huser V, Ahmed W, Carter W, Guan Y, Galvan Y, He X, Rijnbeek P, Hripcsak G, Ryan P, Suchard M.",,No Journal Info,2021,2021-03-01,Y,,,,"

Background:

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

Methods:

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

Findings:

We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice.",,doi:https://doi.org/10.21203/rs.3.rs-279400/v1; html:https://europepmc.org/article/PPR/PPR291347; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR291347&type=FILE&fileName=EMS118164-pdf.pdf&mimeType=application/pdf PPR162356,https://doi.org/10.1101/2020.05.11.20097709,"Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study","Wu J, Huang J, Zhu G, Liu Y, Xiao H, Zhou Q, Si X, Yi H, Wang C, Yang D, Chen S, Liu X, Liu Z, Wang Q, Lv Q, Huang Y, Yu Y, Guan X, Li Y, Nirantharakumar K, Cheng K, Peng S, Xiao H.",,No Journal Info,2020,2020-05-14,Y,,,,"

Background:

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

Methods:

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

Results:

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

Conclusions:

Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.",,doi:https://doi.org/10.1101/2020.05.11.20097709; html:https://europepmc.org/article/PPR/PPR162356; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR162356&type=FILE&fileName=EMS91863-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/14/2020.05.11.20097709.full.pdf +PPR291347,https://doi.org/10.21203/rs.3.rs-279400/v1,Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS,"Prieto-Alhambra D, Kostka K, Duarte-Salles T, Prats-Uribe A, Sena A, Pistillo A, Khalid S, Lai L, Golozar A, Alshammari TM, Dawoud D, Nyberg F, Wilcox A, Andryc A, Williams A, Ostropolets A, Areia C, Jung CY, Harle C, Reich C, Blacketer C, Morales D, Dorr DA, Burn E, Roel E, Tan EH, Minty E, DeFalco F, de Maeztu G, Lipori G, Alghoul H, Zhu H, Thomas J, Bian J, Park J, Roldán JM, Posada J, Banda JM, Horcajada JP, Kohler J, Shah K, Natarajan K, Lynch K, Liu L, Schilling L, Recalde M, Spotnitz M, Gong M, Matheny M, Valveny N, Weiskopf N, Shah N, Alser O, Casajust P, Park RW, Schuff R, Seager S, DuVall S, You SC, Song S, Fernández-Bertolín S, Fortin S, Magoc T, Falconer T, Subbian V, Huser V, Ahmed W, Carter W, Guan Y, Galvan Y, He X, Rijnbeek P, Hripcsak G, Ryan P, Suchard M.",,No Journal Info,2021,2021-03-01,Y,,,,"

Background:

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

Methods:

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

Findings:

We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice.",,doi:https://doi.org/10.21203/rs.3.rs-279400/v1; html:https://europepmc.org/article/PPR/PPR291347; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR291347&type=FILE&fileName=EMS118164-pdf.pdf&mimeType=application/pdf PPR556407,https://doi.org/10.1101/2022.10.07.22280819,A Multi-Granular Stacked Regression for Forecasting Long-Term Demand in Emergency Departments,"James C, Wood R, Denholm R.",,No Journal Info,2022,2022-10-10,Y,,,,"

Background

In the United Kingdom, Emergency Departments (EDs) are under significant pressure due to an ever-increasing number of attendances. Understanding how the capacity of other urgent care services and the health of a population may influence ED attendances is imperative for commissioners and policy makers to develop long-term strategies for reducing this pressure and improving quality and safety.

Methods

We developed a novel Multi-Granular Stacked Regression (MGSR) model using publicly available data to predict future mean monthly ED attendances within Clinical Commissioning Group regions in England. The MGSR combines measures of population health and health service capacity in other related settings. We assessed model performance using the R-squared statistic, measuring variance explained, and the Mean Absolute Percentage Error (MAPE), measuring forecasting accuracy. We used the MGSR to forecast ED demand over a 4-year period under hypothetical scenarios where service capacity is increased, or population health is improved.

Results

Measures of service capacity explain 41 ± 4% of the variance in monthly ED attendances and measures of population health explain 61 ± 25%. The MGSR leads to an overall improvement in performance, with an R-squared of 0.75 ± 0.03 and MAPE of 4% when forecasting mean monthly ED attendances per CCG. Using the MGSR to forecast long-term demand under different scenarios, we found improving population health would reduce peak ED attendances per CCG by approximately 600 per month after 2 years.

Conclusions

Combining models of population health and wider urgent care service capacity for predicting monthly ED attendances leads to an improved performance compared to each model individually. Policies designed to improve population health will reduce ED attendances and enhance quality and safety in the long-term.",,doi:https://doi.org/10.1101/2022.10.07.22280819; html:https://europepmc.org/article/PPR/PPR556407; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR556407&type=FILE&fileName=EMS155538-pdf.pdf&mimeType=application/pdf -PPR319210,https://doi.org/10.1101/2021.04.30.21256119,Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies,"The OpenSAFELY Collaborative, Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ.",,No Journal Info,2021,2021-04-30,Y,,,,"

Objectives

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

Design

Two cohort studies, on behalf of NHS England.

Setting

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

Participants

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

Main outcome measures

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

Results

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

Conclusions

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

Key points

What is already known on this topic

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

What this study adds

In 70,464 people with atrial fibrillation, at the threshold of being treated with an OAC based on risk of stroke, we observed a lower risk of testing positive for SARS-CoV-2 and COVID-19 related deaths associated with routinely prescribed OACs, relative to non-use. This might be explained by OACs preventing severe COVID-19 outcomes, or more cautious behaviours and environmental factors reducing the risk of SARS-CoV-2 infection in those taking OACs. In 372,746 people with non-valvular atrial fibrillation, there was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin compared with DOACs.",,doi:https://doi.org/10.1101/2021.04.30.21256119; html:https://europepmc.org/article/PPR/PPR319210; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR319210&type=FILE&fileName=EMS123890-pdf.pdf&mimeType=application/pdf PPR287050,https://doi.org/10.1101/2021.02.22.21252185,Linked electronic health records for research on a nationwide cohort including over 54 million people in England,"CVD-COVID-UK consortium, Wood A, Denholm R, Hollings S, Cooper J, Ip S, Walker V, Denaxas S, Akbari A, Sterne J, Sudlow C, Wood (chair) A, Denholm R, Hollings S, Cooper J, Ip S, Walker V, Denaxas S, Banerjee A, Whiteley W, Lai A, Priedon R, Sudlow C, Morrice L, Ringham D, Power S, Laidlaw L, Molete M, Walsh J, Coleman G, Day C, Gaffney E, Gentry T, Gray L, Hollings S, Irvine R, Roberts B, Spence E, Waterhouse J, Manuscript drafting and revising, Data wrangling, QA and analysis (including generating phenotype definitions), Figures/graphics, Consortium coordination (BHF Data Science Centre core team), Public and patient advisory panel, NHS Digital (coordination, data management/provision, data access request and information governance support Trusted Research Environment support.",,No Journal Info,2021,2021-02-23,Y,,,,"

ABSTRACT

Objectives

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

Design

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

Setting

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

Participants

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

Main measures of interest

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

Results

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

Conclusions

This population-wide resource demonstrates the importance of linking person-level data across health settings to maximize completeness of key characteristics and to ascertain cardiovascular events and Covid-19 diagnoses. Although established initially to support research on Covid-19 and cardiovascular disease to benefit clinical care and public health and to inform health care policy, it can broaden further to enable a very wide range of research.",,doi:https://doi.org/10.1101/2021.02.22.21252185; html:https://europepmc.org/article/PPR/PPR287050; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR287050&type=FILE&fileName=EMS117369-pdf.pdf&mimeType=application/pdf +PPR319210,https://doi.org/10.1101/2021.04.30.21256119,Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies,"The OpenSAFELY Collaborative, Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ.",,No Journal Info,2021,2021-04-30,Y,,,,"

Objectives

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

Design

Two cohort studies, on behalf of NHS England.

Setting

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

Participants

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

Main outcome measures

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

Results

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

Conclusions

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

Key points

What is already known on this topic

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

What this study adds

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

Background

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

Methods

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

Findings

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

Interpretation

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

Many of the groups with the lowest rates of COVID-19 vaccination are also the groups that have been disproportionately affected by the pandemic, including severe illness and mortality. Research is urgently needed to understand why these disparities exist and how they can be addressed, for example through public health or community engagement programmes. Since the relationships between sociodemographic characteristics and vaccination coverage may differ by age group, it is important for future research to disaggregate by age group when examining these inequalities.",,doi:https://doi.org/10.1101/2021.10.07.21264681; html:https://europepmc.org/article/PPR/PPR404742; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR404742&type=FILE&fileName=EMS136793-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/07/2021.10.07.21264681.full.pdf PPR180964,https://doi.org/10.1101/2020.06.26.20140921,Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank,"Hastie CE, Pell JP, Sattar N.",,No Journal Info,2020,2020-06-28,N,,,,"

Purpose

Vitamin D has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants.

Methods

UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection.

Results

Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. Vitamin D was associated with severe COVID-19 infection and mortality univariably (mortality HR=0.99; 95% CI 0.98-0.998; p =0.016), but not after adjustment for confounders (mortality HR=0.998; 95% CI=0.99-1.01; p =0.696).

Conclusions

Our findings do not support a potential link between vitamin D concentrations and risk of severe COVID-19 infection and mortality. Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.",,doi:https://doi.org/10.1101/2020.06.26.20140921; html:https://europepmc.org/article/PPR/PPR180964; doi:https://doi.org/10.1101/2020.06.26.20140921 PPR152986,https://doi.org/10.1101/2020.04.16.20067504,"“The Effect of Inter-City Travel Restrictions on Geographical Spread of COVID-19: Evidence from Wuhan, China”","Quilty BJ, Diamond C, Liu Y, Gibbs H, Russell TW, Jarvis CI, Prem K, Pearson CA, Clifford S, Flasche S, Klepac P, Eggo RM, Jit M, CMMID COVID-19 working group.",,No Journal Info,2020,2020-04-21,Y,,,,"

Summary

Background

To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020, restricting travel to other parts of China. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China.

Methods

We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to March 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios representing the effect of local non-pharmaceutical interventions.

Findings

In the four cities, given the potentially high prevalence of COVID-19 in Wuhan between Dec 2019 and early Jan 2020, local transmission may have been seeded as early as 2 - 8 January 2020. By the time the cordon sanitaire was imposed, simulated case counts were likely in the hundreds. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities.

Interpretation

Our results indicate that the cordon sanitaire may not have prevented COVID-19 spread in major Chinese cities; local non-pharmaceutical interventions were likely more important for this.

Research in Context

Evidence before this study

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in Wuhan, China. In response to the outbreak, authorities enacted a cordon sanitaire in order to limit spread. Several studies have sought to determine the efficacy of the policy; a search of PubMed for “coronavirus AND (travel restrictions OR travel ban OR shutdown OR cordon sanitaire) AND (Wuhan OR China)” returned 24 results. However other studies have relied on reported cases to determine efficacy, which are likely subject to reporting and testing biases. Early outbreak dynamics are also subject to a significant degree of stochastic uncertainty due to small numbers of cases.

Added value of this study

Here we use publicly-available mobility data and a stochastic branching process model to evaluate the efficacy of the cordon sanitaire to limiting the spread of COVID-19 from Wuhan to other cities in mainland China, while accounting for underreporting and uncertainty. We find that although travel restrictions led to a significant decrease in the number of individuals leaving Wuhan during the busy post-Lunar New Year holiday travel period, local transmission was likely already established in major cities. Thus, the travel restrictions likely did not affect the epidemic trajectory substantially in these cities.

Implications of all the available evidence

A cordon sanitaire around the epicentre alone may not be able to reduce COVID-19 incidence when implemented after local transmission has occurred in highly connected neighbors. Local non-pharmaceutical interventions to reduce transmissibility (e.g., school and workplace closures) may have contributed more to the observed decrease in incidence in mainland China.",Quilty et al attempted to understand the effectiveness of inter-city travel restrictions on spread of COVID-19 in Wuhan. The results indicate that the cordon sanitaire may not have prevented COVID-19 spread in major Chinese cities; local non-pharmaceutical interventions were likely more important for this.,doi:https://doi.org/10.1101/2020.04.16.20067504; html:https://europepmc.org/article/PPR/PPR152986; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR152986&type=FILE&fileName=EMS90479-pdf.pdf&mimeType=application/pdf PPR160805,https://doi.org/10.1101/2020.05.07.20093849,The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak,"Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, Knight GM, Eggo RM, Kucharski AJ, Funk S, Flasche S, Houben RMGJ, CMMID 2019-nCoV working group.",,No Journal Info,2020,2020-05-11,Y,Transmission; Asymptomatic Infections; Covid-19; Sars-cov-2,,,"

Background

Some key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship.

Methods

We used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals.

Findings

On the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15.

Interpretation

Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19.

Funding

ERC Starting Grant (#757699), Wellcome trust (208812/Z/17/Z), HDR UK (MR/S003975/1)",The work investigates the cases of COVID-19 recorded on the diamond princess cruise ship. The work identifies that many cases were asymptomatic and are likely to contribute to transmission.,doi:https://doi.org/10.1101/2020.05.07.20093849; html:https://europepmc.org/article/PPR/PPR160805; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR160805&type=FILE&fileName=EMS86859-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.7554/elife.58699 PPR387421,https://doi.org/10.1101/2021.08.18.21262222,"Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: whole population cohort study in 46 million adults in England","CVD-COVID-UK consortium, Whiteley WN, Ip S, Cooper JA, Bolton T, Keene S, Walker V, Denholm R, Akbari A, Omigie E, Hollings S, Di Angelantonio E, Denaxas S, Wood A, Sterne JAC, Sudlow C, Writing committee.",,No Journal Info,2021,2021-08-23,Y,,,,"

ABSTRACT

Background

Thromboses in unusual locations after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed.

Methods

We analysed linked electronic health records from adults living in England, from 8 th December 2020 to 18 th March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years, and adjusted for age, sex, comorbidities, and social and demographic factors.

Results

Of 46,162,942 adults, 21,193,814 (46%) had their first vaccination during follow-up. Adjusted HRs 1-28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 respectively, were 0.97 (95% CI: 0.90-1.05) and 0.58 (0.53–0.63) for venous thromboses, and 0.90 (0.86-0.95) and 0.76 (0.73-0.79) for arterial thromboses. Corresponding HRs for BNT162b2 were 0.81 (0.74–0.88) and 0.57 (0.53–0.62) for venous thromboses, and 0.94 (0.90-0.99) and 0.72 (0.70-0.75) for arterial thromboses. HRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and thrombocytopenia in adults aged <70 years were higher 1-28 days after ChAdOx1-S (adjusted HRs 2.27, 95% CI:1.33– 3.88 and 1.71, 1.35–2.16 respectively), but not after BNT162b2 (0.59, 0.24–1.45 and 1.00, 0.75–1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1-28 days after ChAdOx1-S were 0.9–3 per million, varying by age and sex.

Conclusions

Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.",,doi:https://doi.org/10.1101/2021.08.18.21262222; html:https://europepmc.org/article/PPR/PPR387421; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR387421&type=FILE&fileName=EMS134400-pdf.pdf&mimeType=application/pdf; pdf:https://cronfa.swan.ac.uk/Record/cronfa57688/Download/57688__23941__69a222d696ec4cd991ed01d7cb47ee8e.pdf PPR179288,https://doi.org/10.1101/2020.06.22.20137273,Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report,"Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ, RECOVERY Collaborative Group.",,No Journal Info,2020,2020-06-22,Y,,,,"

ABSTRACT

Background

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

Methods

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

Results

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

Conclusions

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

Trial registrations

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

Funding

Medical Research Council and National Institute for Health Research (Grant ref: MC_PC_19056).",,doi:https://doi.org/10.1101/2020.06.22.20137273; html:https://europepmc.org/article/PPR/PPR179288; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR179288&type=FILE&fileName=EMS88343-pdf.pdf&mimeType=application/pdf; pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2021436?articleTools=true -PPR191930,https://doi.org/10.1101/2020.07.24.20161281,Strategies to reduce the risk of SARS-CoV-2 re-introduction from international travellers,"Clifford S, Quilty BJ, Russell TW, Liu Y, Chan YD, Pearson CAB, Eggo RM, Endo A, Flasche S, Edmunds WJ, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-07-24,Y,,,,"

Summary

To mitigate SARS-CoV-2 transmission risks from international travellers, many countries currently use a combination of up to 14 days of self-quarantine on arrival and testing for active infection. We used a simulation model of air travellers arriving to the UK from the EU or the USA and the timing of their stages of infection to evaluate the ability of these strategies to reduce the risk of seeding community transmission. We find that a quarantine period of 8 days on arrival with a PCR test on day 7 (with a 1-day delay for test results) can reduce the number of infectious arrivals released into the community by a median 94% compared to a no quarantine, no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median 99% reduction). Shorter quarantine periods still can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (the mean incubation period) in quarantine and have at least one negative test before release are highly effective (e.g. a test on day 5 with release on day 6 results in a median 88% reduction in transmission potential). Without intervention, the current high prevalence in the US (40 per 10,000) results in a higher expected number of infectious arrivals per week (up to 23) compared to the EU (up to 12), despite an estimated 8 times lower volume of travel in July 2020. Requiring a 14-day quarantine period likely results in less than 1 infectious traveller each entering the UK per week from the EU and the USA (97.5th percentile). We also find that on arrival the transmission risk is highest from pre-symptomatic travellers; quarantine policies will shift this risk increasingly towards asymptomatic infections if eventually-symptomatic individuals self-isolate after the onset of symptoms. As passenger numbers recover, strategies to reduce the risk of re-introduction should be evaluated in the context of domestic SARS-CoV-2 incidence, preparedness to manage new outbreaks, and the economic and psychological impacts of quarantine.",,doi:https://doi.org/10.1101/2020.07.24.20161281; html:https://europepmc.org/article/PPR/PPR191930; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR191930&type=FILE&fileName=EMS87861-pdf.pdf&mimeType=application/pdf PPR252028,https://doi.org/10.1101/2020.12.08.20246231,Artificial intelligence-enabled analysis of UK and US public attitudes on Facebook and Twitter towards COVID-19 vaccinations,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,No Journal Info,2020,2020-12-11,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

AI-enabled social-media analysis should be considered for adoption by institutions and governments, alongside surveys and other conventional methods of assessing public attitude. This could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccinations, help address concerns of vaccine-sceptics and develop more effective policies and communication strategies to maximise uptake.",,doi:https://doi.org/10.1101/2020.12.08.20246231; html:https://europepmc.org/article/PPR/PPR252028; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR252028&type=FILE&fileName=EMS108377-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/11/2020.12.08.20246231.full.pdf +PPR191930,https://doi.org/10.1101/2020.07.24.20161281,Strategies to reduce the risk of SARS-CoV-2 re-introduction from international travellers,"Clifford S, Quilty BJ, Russell TW, Liu Y, Chan YD, Pearson CAB, Eggo RM, Endo A, Flasche S, Edmunds WJ, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-07-24,Y,,,,"

Summary

To mitigate SARS-CoV-2 transmission risks from international travellers, many countries currently use a combination of up to 14 days of self-quarantine on arrival and testing for active infection. We used a simulation model of air travellers arriving to the UK from the EU or the USA and the timing of their stages of infection to evaluate the ability of these strategies to reduce the risk of seeding community transmission. We find that a quarantine period of 8 days on arrival with a PCR test on day 7 (with a 1-day delay for test results) can reduce the number of infectious arrivals released into the community by a median 94% compared to a no quarantine, no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median 99% reduction). Shorter quarantine periods still can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (the mean incubation period) in quarantine and have at least one negative test before release are highly effective (e.g. a test on day 5 with release on day 6 results in a median 88% reduction in transmission potential). Without intervention, the current high prevalence in the US (40 per 10,000) results in a higher expected number of infectious arrivals per week (up to 23) compared to the EU (up to 12), despite an estimated 8 times lower volume of travel in July 2020. Requiring a 14-day quarantine period likely results in less than 1 infectious traveller each entering the UK per week from the EU and the USA (97.5th percentile). We also find that on arrival the transmission risk is highest from pre-symptomatic travellers; quarantine policies will shift this risk increasingly towards asymptomatic infections if eventually-symptomatic individuals self-isolate after the onset of symptoms. As passenger numbers recover, strategies to reduce the risk of re-introduction should be evaluated in the context of domestic SARS-CoV-2 incidence, preparedness to manage new outbreaks, and the economic and psychological impacts of quarantine.",,doi:https://doi.org/10.1101/2020.07.24.20161281; html:https://europepmc.org/article/PPR/PPR191930; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR191930&type=FILE&fileName=EMS87861-pdf.pdf&mimeType=application/pdf PPR208611,https://doi.org/10.1101/2020.09.02.20185173,"Characteristics and outcomes of 627 044 COVID-19 patients with and without obesity in the United States, Spain, and the United Kingdom","Recalde M, Roel E, Pistillo A, Sena AG, Prats-Uribe A, Ahmed W, Alghoul H, Alshammari TM, Alser O, Areia C, Burn E, Casajust P, Dawoud D, DuVall SL, Falconer T, Fernández-Bertolín S, Golozar A, Gong M, Lai LYH, Lane JC, Lynch KE, Matheny ME, Mehta PP, Morales DR, Natarjan K, Nyberg F, Posada JD, Reich CG, Schilling LM, Shah K, Shah NH, Subbian V, Zhang L, Zhu H, Ryan P, Prieto-Alhambra D, Kostka K, Duarte-Salles T.",,No Journal Info,2020,2020-09-03,Y,,,,"

Background

COVID-19 may differentially impact people with obesity. We aimed to describe and compare the demographics, comorbidities, and outcomes of obese patients with COVID-19 to those of non-obese patients with COVID-19, or obese patients with seasonal influenza.

Methods

We conducted a cohort study based on outpatient/inpatient care, and claims data from January to June 2020 from the US, Spain, and the UK. We used six databases standardized to the OMOP common data model. We defined two cohorts of patients diagnosed and/or hospitalized with COVID-19. We created corresponding cohorts for patients with influenza in 2017-2018. We followed patients from index date to 30 days or death. We report the frequency of socio-demographics, prior comorbidities, and 30-days outcomes (hospitalization, events, and death) by obesity status.

Findings

We included 627 044 COVID-19 (US: 502 650, Spain: 122 058, UK: 2336) and 4 549 568 influenza (US: 4 431 801, Spain: 115 224, UK: 2543) patients. The prevalence of obesity was higher among hospitalized COVID-19 (range: 38% to 54%) than diagnosed COVID-19 (30% to 47%), or diagnosed (15% to 47%) or hospitalized (27% to 48%) influenza patients. Obese hospitalized COVID-19 patients were more often female and younger than non-obese COVID-19 patients or obese influenza patients. Obese COVID-19 patients were more likely to have prior comorbidities, present with cardiovascular and respiratory events during hospitalization, require intensive services, or die compared to non-obese COVID-19 patients. Obese COVID-19 patients were more likely to require intensive services or die compared to obese influenza patients, despite presenting with fewer comorbidities.

Interpretation

We show that obesity is more common amongst COVID-19 than influenza patients, and that obese patients present with more severe forms of COVID-19 with higher hospitalization, intensive services, and fatality than non-obese patients. These data are instrumental for guiding preventive strategies of COVID-19 infection and complications.

Funding

The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, and IQVIA. The University of Oxford received funding related to this work from the Bill & Melinda Gates Foundation (Investment ID INV-016201 and INV-019257). APU has received funding from the Medical Research Council (MRC) [MR/K501256/1, MR/N013468/1] and Fundación Alfonso Martín Escudero (FAME) (APU). VINCI [VA HSR RES 13-457] (SLD, MEM, KEL). JCEL has received funding from the Medical Research Council (MR/K501256/1) and Versus Arthritis (21605). No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, Department of Veterans Affairs or the United States Government, NHS, or the Department of Health, England.

Research in context

Evidence before this study

Previous evidence suggests that obese individuals are a high risk population for COVID-19 infection and complications. We searched PubMed for articles published from December 2019 until June 2020, using terms referring to SARS-CoV-2 or COVID-19 combined with terms for obesity. Few studies reported obesity and most of them were limited by small sample sizes and restricted to hospitalized patients. Further, they used different definitions for obesity (i.e. some reported together overweight and obesity, others only reported obesity with BMI>40kg/m 2 ). To date, no study has provided detailed information on the characteristics of obese COVID-19 patients, such as the prevalence of comorbidities or COVID-19 related outcomes. In addition, despite the fact that COVID-19 has been often compared to seasonal influenza, there are no studies assessing whether obese patients with COVID-19 differ from obese patients with seasonal influenza.

Added value of this study

We report the largest cohort of obese patients with COVID-19 and provide information on more than 29 000 aggregate characteristics publicly available. Our findings were consistent across the participating databases and countries. We found that the prevalence of obesity is higher among COVID-19 compared to seasonal influenza patients. Obese patients with COVID-19 are more commonly female and have worse outcomes than non-obese patients. Further, they have worse outcomes than obese patients with influenza, despite presenting with fewer comorbidities.

Implications of all the available evidence

Our results show that individuals with obesity present more comorbidities and worse outcomes for COVID-19 than non-obese patients. These findings may be useful in guiding clinical practice and future preventative strategies for obese individuals, as well as provide useful data to support subsequent association studies focussed on obesity and COVID-19.",,doi:https://doi.org/10.1101/2020.09.02.20185173; html:https://europepmc.org/article/PPR/PPR208611; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR208611&type=FILE&fileName=EMS94639-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/09/03/2020.09.02.20185173.full.pdf PPR369660,https://doi.org/10.1101/2021.07.09.21260272,Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region,"Liu Y, Sandmann FG, Barnard RC, Pearson CA, Pastore R, Pebody R, Flasche S, Jit M, CMMID COVID-19 Working Group.",,No Journal Info,2021,2021-07-14,Y,,,,"

Background

Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine roll-out speed. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region.

Methods

We fitted country-specific age-stratified compartmental transmission models to reported COVID-19 mortality in the WHO European Region to inform the immunity level before vaccine roll-out. Building upon broad recommendations from the WHO Strategic Advisory Group of Experts on Immunisation (SAGE), we examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incremental expansion to successively younger five-year age groups. We explored four roll-out scenarios based on projections or recent observations (R1-4) - the slowest scenario (R1) covers 30% of the total population by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy (cLE), comorbidity- and quality-adjusted life years (cQALY), and the value of human capital (HC). Six sets of infection-blocking and disease-reducing vaccine efficacies were considered.

Findings

The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics and roll-out speeds. Overall, V60 consistently performed better than or comparably to V75. There were greater benefits in prioritising older adults when roll-out is slow and when VE is low. Under faster roll-out, V+ was the most desirable option.

Interpretation

A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults.

Funding

World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust

Research in Context

Evidence before this study

We searched PubMed and medRxiv for articles published in English from inception to 9 Jun 2021, with the search terms: (“COVID-19” OR “SARS-CoV-2”) AND (“priorit*) AND (“model*”) AND (“vaccin*”) and identified 66 studies on vaccine prioritization strategies. Of the 25 studies that compared two or more age-based prioritisation strategies, 12 found that targeting younger adults minimised infections while targeting older adults minimised mortality; an additional handful of studies found similar outcomes between different age-based prioritisation strategies where large outbreaks had already occurred. However, only two studies have explored age-based vaccine prioritisation using models calibrated to observed outbreaks in more than one country, and no study has explored the effectiveness of vaccine prioritisation strategies across settings with different population structures, contact patterns, and outbreak history.

Added-value of this study

We evaluated various age-based vaccine prioritisation strategies for 38 countries in the WHO European Region using various health and economic outcomes for decision-making, by parameterising models using observed outbreak history, known epidemiologic and vaccine characteristics, and a range of realistic vaccine roll-out scenarios. We showed that while targeting older adults was generally advantageous, broadly targeting everyone above 60 years might perform better than or comparably to a more detailed strategy that targeted the oldest age group above 75 years followed by those in the next younger five-year age band. Rapid vaccine roll-out has only been observed in a small number of countries. If vaccine coverage can reach 80% by the end of 2021, prioritising older adults may not be optimal in terms of health and economic impact. Lower vaccine efficacy was associated with greater relative benefits only under relatively slow roll-out scenarios considered.

Implication of all the available evidence

COVID-19 vaccine prioritization strategies that require more precise targeting of individuals of a specific and narrow age range may not necessarily lead to better outcomes compared to strategies that prioritise populations across broader age ranges. In the WHO European Region, prioritising all adults equally or younger adults first will only optimise health and economic impact when roll-out is rapid, which may raise between-country equity issues given the global demand for COVID-19 vaccines.",,doi:https://doi.org/10.1101/2021.07.09.21260272; html:https://europepmc.org/article/PPR/PPR369660; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR369660&type=FILE&fileName=EMS130637-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.1016/j.lanepe.2021.100267 PPR247301,https://doi.org/10.1101/2020.11.27.20238147,"Ethnicity, Household Composition and COVID-19 Mortality: A National Linked Data Study","Nafilyan V, Islam N, Ayoubkhani D, Gilles C, Katikireddi SV, Mathur R, Summerfield A, Tingay K, Tingay K, Asaria M, John A, Goldblatt P, Banerjee A, Khunti K.",,No Journal Info,2020,2020-12-02,Y,,,,"

Background

Ethnic minorities have experienced disproportionate COVID-19 mortality rates. We estimated associations between household composition and COVID-19 mortality in older adults (≥ 65 years) using a newly linked census-based dataset, and investigated whether living in a multi-generational household explained some of the elevated COVID-19 mortality amongst ethnic minority groups.

Methods

Using retrospective data from the 2011 Census linked to Hospital Episode Statistics (2017-2019) and death registration data (up to 27 th July 2020), we followed adults aged 65 years or over living in private households in England from 2 March 2020 until 27 July 2020 (n=10,078,568). We estimated hazard ratios (HRs) for COVID-19 death for people living in a multi-generational household compared with people living with another older adult, adjusting for geographical factors, socio-economic characteristics and pre-pandemic health. We conducted a causal mediation analysis to estimate the proportion of ethnic inequalities explained by living in a multi-generational household.

Results

Living in a multi-generational household was associated with an increased risk of COVID-19 death. After adjusting for confounding factors, the HRs for living in a multi-generational household with dependent children were 1.13 [95% confidence interval 1.01-1.27] and 1.17 [1.01-1.35] for older males and females. The HRs for living in a multi-generational household without dependent children were 1.03 [0.97 - 1.09] for older males and 1.22 [1.12 - 1.32] for older females. Living in a multi-generational household explained between 10% and 15% of the elevated risk of COVID-19 death among older females from South Asian background, but very little for South Asian males or people in other ethnic minority groups.

Conclusion

Older adults living with younger people are at increased risk of COVID-19 mortality, and this is a notable contributing factor to the excess risk experienced by older South Asian females compared to White females. Relevant public health interventions should be directed at communities where such multi-generational households are highly prevalent.

Funding

This research was funded by the Office for National Statistics.",,doi:https://doi.org/10.1101/2020.11.27.20238147; html:https://europepmc.org/article/PPR/PPR247301; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR247301&type=FILE&fileName=EMS107607-pdf.pdf&mimeType=application/pdf @@ -300,8 +300,8 @@ PPR184933,https://doi.org/10.1101/2020.07.07.20148460,Reconstructing the early g PPR265407,https://doi.org/10.1101/2021.01.12.21249672,"Characteristics and outcomes of 118,155 COVID-19 individuals with a history of cancer in the United States and Spain","Roel E, Pistillo A, Recalde M, Sena AG, Fernández-Bertolín S, Aragón M, Puente D, Ahmed W, Alghoul H, Alser O, Alshammari TM, Areia C, Blacketer C, Carter W, Casajust P, Culhane AC, Dawoud D, DeFalco F, Duvall SL, Falconer T, Golozar A, Gong M, Hester L, Hripcsak G, Tan EH, Jeon H, Jonnagaddala J, Lai LY, Lynch KE, Matheny ME, Morales DR, Natarajan K, Nyberg F, Ostropolets A, Posada JD, Prats-Uribe A, Reich CG, Rivera D, Schilling LM, Soerjomataram I, Shah K, Shah N, Shen Y, Spotniz M, Subbian V, Suchard MA, Trama A, Zhang L, Zhang Y, Ryan P, Prieto-Alhambra D, Kostka K, Duarte-Salles T.",,No Journal Info,2021,2021-01-15,Y,,,,"

Purpose

We aimed to describe the demographics, cancer subtypes, comorbidities and outcomes of patients with a history of cancer with COVID-19 from March to June 2020. Secondly, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza.

Methods

We conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: i) diagnosed with COVID-19, ii) hospitalized with COVID-19, and iii) hospitalized with influenza in 2017-2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes.

Results

We included 118,155 patients with a cancer history in the COVID-19 diagnosed and 41,939 in the COVID-19 hospitalized cohorts. The most frequent cancer subtypes were prostate and breast cancer (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies were also frequent, with non-Hodgkin’s lymphoma being among the 5 most common cancer subtypes in the diagnosed cohort. Overall, patients were more frequently aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 8% to 14% and from 18% to 26% in the diagnosed and h ospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n=242,960) had a similar distribution of cancer subtypes, sex, age and comorbidities but lower occurrence of adverse events.

Conclusion

Patients with a history of cancer and COVID-19 have advanced age, multiple comorbidities, and a high occurence of COVID-19-related events. Additionaly, hematological malignancies were frequent in these patients.This observational study provides epidemiologic characteristics that can inform clinical care and future etiological studies.",,doi:https://doi.org/10.1101/2021.01.12.21249672; html:https://europepmc.org/article/PPR/PPR265407; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR265407&type=FILE&fileName=EMS110647-pdf.pdf&mimeType=application/pdf PPR152293,https://doi.org/10.1101/2020.04.14.20065417,Clinical academic research in the time of Corona: a simulation study in England and a call for action,"Banerjee A, Katsoulis M, Lai AG, Pasea L, Treibel TA, Manisty C, Denaxas S, Quarta G, Hemingway H, Cavalcante J, Noursadeghi M, Moon JC.",,No Journal Info,2020,2020-04-17,Y,,,,"

Background

Coronavirus (COVID-19) poses health system challenges in every country. As with any public health emergency, a major component of the global response is timely, effective science. However, particular factors specific to COVID-19 must be overcome to ensure that research efforts are optimised. We aimed to model the impact of COVID-19 on the clinical academic response in the UK, and to provide recommendations for COVID-related research.

Methods

We constructed a simple stochastic model to determine clinical academic capacity in the UK in four policy approaches to COVID-19 with differing population infection rates: “Italy model” (6%), “mitigation” (10%), “relaxed mitigation” (40%) and “do-nothing” (80%) scenarios. The ability to conduct research in the COVID-19 climate is affected by the following key factors: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics).

Findings

In “Italy model”, “mitigation”, “relaxed mitigation” and “do-nothing” scenarios, from 5 March 2020 the duration (days) and peak infection rates (%) are 95(2.4%), 115(2.5%), 240(5.3%) and 240(16.7%) respectively. Near complete attrition of academia (87% reduction, <400 clinical academics) occurs 35 days after pandemic start for 11, 34, 62, 76 days respectively – with no clinical academics at all for 37 days in the “do-nothing” scenario. Restoration of normal academic workforce (80% of normal capacity) takes 11,12, 30 and 26 weeks respectively.

Interpretation

Pandemic COVID-19 crushes the science needed at system level. National policies mitigate, but the academic community needs to adapt. We highlight six key strategies: radical prioritisation (eg 3-4 research ideas per institution), deep resourcing, non-standard leadership (repurposing of key non-frontline teams), rationalisation (profoundly simple approaches), careful site selection (eg protected sites with large academic backup) and complete suspension of academic competition with collaborative approaches.",,doi:https://doi.org/10.1101/2020.04.14.20065417; html:https://europepmc.org/article/PPR/PPR152293; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR152293&type=FILE&fileName=EMS90070-pdf.pdf&mimeType=application/pdf PPR538641,https://doi.org/10.1101/2022.08.29.22279351,Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong,"Ali ST, Chen D, Lim WW, Yeung A, Adam DC, Lau YC, Lau EHY, Wong JY, Xiao J, Ho F, Gao H, Wang L, Xu X, Du Z, Wu P, Leung GM, Cowling BJ.",,No Journal Info,2022,2022-08-30,Y,,,,"The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number “ R t ”, a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of R t , and provided additional insights into the impact of public health measures on transmission of infections.

One-Sentence Summary

Real-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.",,doi:https://doi.org/10.1101/2022.08.29.22279351; html:https://europepmc.org/article/PPR/PPR538641; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR538641&type=FILE&fileName=EMS153686-pdf.pdf&mimeType=application/pdf -PPR558613,https://doi.org/10.1101/2022.10.17.22281058,Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults’ primary care records through OpenSAFELY,"Fisher L, Curtis HJ, Croker R, Wiedemann M, Speed V, Wood C, Brown A, Hopcroft LE, Higgins R, Massey J, Inglesby P, Morton CE, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Macdonald O, Lewis T, Wood M, Myers M, Samuel M, Conibere R, Baqir W, Sood H, Drury C, Collison K, Bates C, Evans D, Dillingham I, Ward T, Davy S, Smith RM, Hulme W, Green A, Parry J, Hester F, Harper S, Cockburn J, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, MacKenna B, Goldacre B.",,No Journal Info,2022,2022-10-17,Y,,,,"

Background

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

Objectives

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

Methods

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

Results

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

Conclusions

The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.",,doi:https://doi.org/10.1101/2022.10.17.22281058; html:https://europepmc.org/article/PPR/PPR558613; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558613&type=FILE&fileName=EMS155818-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.1101/2022.10.17.22281058 PPR530179,https://doi.org/10.1101/2022.08.08.22278493,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,No Journal Info,2022,2022-08-09,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnicity remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.",,doi:https://doi.org/10.1101/2022.08.08.22278493; html:https://europepmc.org/article/PPR/PPR530179; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR530179&type=FILE&fileName=EMS152515-pdf.pdf&mimeType=application/pdf; pdf:https://orca.cardiff.ac.uk/id/eprint/157897/1/12889_2023_Article_15345.pdf +PPR558613,https://doi.org/10.1101/2022.10.17.22281058,Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults’ primary care records through OpenSAFELY,"Fisher L, Curtis HJ, Croker R, Wiedemann M, Speed V, Wood C, Brown A, Hopcroft LE, Higgins R, Massey J, Inglesby P, Morton CE, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Macdonald O, Lewis T, Wood M, Myers M, Samuel M, Conibere R, Baqir W, Sood H, Drury C, Collison K, Bates C, Evans D, Dillingham I, Ward T, Davy S, Smith RM, Hulme W, Green A, Parry J, Hester F, Harper S, Cockburn J, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, MacKenna B, Goldacre B.",,No Journal Info,2022,2022-10-17,Y,,,,"

Background

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

Objectives

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

Methods

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

Results

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

Conclusions

The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.",,doi:https://doi.org/10.1101/2022.10.17.22281058; html:https://europepmc.org/article/PPR/PPR558613; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558613&type=FILE&fileName=EMS155818-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.1101/2022.10.17.22281058 PPR300650,https://doi.org/10.1101/2021.03.17.21253853,"Modelling the impact of rapid tests, tracing and distancing in lower-income countries suggest that optimal policies vary with rural-urban settings","Jiang X, Gong W, Dobreva Z, Gao Y, Quaife M, Fraser C, Holmes C.",,No Journal Info,2021,2021-03-20,Y,,,,"Low- and middle-income countries (LMICs) remain of high potential for hotspots for COVID-19 deaths and emerging variants given the inequality of vaccine distribution and their vulnerable healthcare systems. We aim to evaluate containment strategies that are sustainable and effective for LMICs. We constructed synthetic populations with varying contact and household structures to capture LMIC demographic characteristics that vary across communities. Using an agent- based model, we explored the optimal containment strategies for rural and urban communities by designing and simulating setting-specific strategies that deploy rapid diagnostic tests, symptom screening, contact tracing and physical distancing. In low-density rural communities, we found implementing either high quality (sensitivity > 50%) antigen rapid diagnostic tests or moderate physical distancing could contain the transmission. In urban communities, we demonstrated that both physical distancing and case finding are essential for containing COVID-19 (average infection rate < 10%). In high density communities that resemble slums and squatter settlements, physical distancing is less effective compared to rural and urban communities. Lastly, we demonstrated contact tracing is essential for effective containment. Our findings suggested that rapid diagnostic tests could be prioritised for control and monitor COVID-19 transmission and highlighted that contact survey data could guide strategy design to save resources for LMICs. An accompanying open source R package is available for simulating COVID-19 transmission based on contact network models.",,doi:https://doi.org/10.1101/2021.03.17.21253853; html:https://europepmc.org/article/PPR/PPR300650; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR300650&type=FILE&fileName=EMS120357-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/08/2021.03.17.21253853.full.pdf PPR443779,https://doi.org/10.1101/2022.01.16.22269146,Development and validation of the Symptom Burden Questionnaire™ for Long Covid: A Rasch analysis,"Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",,No Journal Info,2022,2022-01-17,Y,,,,"

ABSTRACT

Objective

To describe the development and initial validation of a novel patient-reported outcome measure of Long COVID symptom burden, the Symptom-Burden Questionnaire for Long COVID (SBQ™-LC).

Method and Findings

This multi-phase, prospective mixed-methods study took place between April and August 2021 in the United Kingdom (UK). A conceptual framework and initial item pool were developed from published systematic reviews. Further concept elicitation and content validation was undertaken with adults with lived experience (n = 13) and clinicians (n = 10), and face validity was confirmed by the Therapies for Long COVID Study Patient and Public Involvement group (n = 25). The draft SBQ™-LC was field tested by adults with self-reported Long COVID recruited via social media and international Long COVID support groups (n = 274). Thematic analysis of interview and survey transcripts established content validity and informed construction of the draft questionnaire. Rasch analysis of field test data guided item and scale refinement and provided evidence of the final SBQ™-LC’s measurement properties. The Rasch-derived SBQ™-LC is composed of 17 independent scales with promising psychometric properties. Respondents rate symptom burden during the past 7-days using a dichotomous response or 4-point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that may be converted to a linear (0 – 100) score. Higher scores represent higher symptom burden.

Conclusions

The SBQ™-LC is a comprehensive patient-reported assessment of Long COVID symptom burden developed using modern psychometric methods. It measures symptoms of Long COVID important to individuals with lived experience and may be used to evaluate the impact of interventions and inform best practice in clinical management.",,doi:https://doi.org/10.1101/2022.01.16.22269146; html:https://europepmc.org/article/PPR/PPR443779; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR443779&type=FILE&fileName=EMS159917-pdf.pdf&mimeType=application/pdf PPR150874,https://doi.org/10.1101/2020.04.10.20059121,"ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study","Gill D, Arvanitis M, Carter P, Hernández Cordero AI, Jo B, Karhunen V, Larsson SC, Li X, Lockhart SM, Mason A, Pashos E, Saha A, Tan VY, Zuber V, Bossé Y, Fahle S, Hao K, Jiang T, Joubert P, Lunt AC, Ouwehand WH, Roberts DJ, Timens W, van den Berge M, Watkins NA, Battle A, Butterworth AS, Danesh J, Engelhardt BE, Peters JE, Sin DD, Burgess S.",,No Journal Info,2020,2020-04-14,Y,,,,"

Objectives

To use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to provide insight into how these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels.

Design

Two-sample Mendelian randomization (MR) analysis.

Setting

Summary:

-level genetic association data.

Participants

Participants were predominantly of European ancestry. Variants that proxy ACE inhibitor drug effects and cardiometabolic risk factors (body mass index, chronic obstructive pulmonary disease, lifetime smoking index, low-density lipoprotein cholesterol, systolic blood pressure and type 2 diabetes mellitus) were selected from publicly available genome-wide association study data (sample sizes ranging from 188,577 to 898,130 participants). Genetic association estimates for lung expression of ACE2 and TMPRSS2 were obtained from the Gene-Tissue Expression (GTEx) project (515 participants) and the Lung eQTL Consortium (1,038 participants). Genetic association estimates for circulating plasma ACE2 levels were obtained from the INTERVAL study (4,947 participants).

Main outcomes and measures

Lung ACE2 and TMPRSS2 expression and plasma ACE2 levels.

Results

There were no association of genetically proxied ACE inhibition with any of the outcomes considered here. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in GTEx (p = 4×10 −4 ) and with circulating plasma ACE2 levels in INTERVAL (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations between genetically predicted levels of the other cardiometabolic traits with the outcomes.

Conclusions

This study does not provide evidence to support that ACE inhibitor antihypertensive drugs affect lung ACE2 and TMPRSS2 expression or plasma ACE2 levels. In the current COVID-19 pandemic, our findings do not support a change in ACE inhibitor medication use without clinical justification.

Summary boxes

What is already known on this topic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Serine protease TMPRSS2 is involved in priming the SARS-CoV-2 spike protein for cellular entry through the angiotensin-converting enzyme 2 (ACE2) receptor. Expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for risk of SARS-CoV-2 infection and severity of COVID-19.

What this study adds

We used human genetic variants that proxy ACE inhibitor drug effects and cardiometabolic risk factors to provide insight into how these exposures affect lung ACE2 and TMPRSS2 expression and circulating ACE2 levels. Our findings do not support the hypothesis that ACE inhibitors have effects on ACE2 expression. We found some support for an association of genetic liability to type 2 diabetes mellitus with higher lung ACE2 expression and plasma ACE2 levels, but evidence was inconsistent across studies.",,doi:https://doi.org/10.1101/2020.04.10.20059121; html:https://europepmc.org/article/PPR/PPR150874; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR150874&type=FILE&fileName=EMS90119-pdf.pdf&mimeType=application/pdf; pdf:https://europepmc.org/articles/pmc7735342?pdf=render @@ -326,10 +326,10 @@ PPR157903,https://doi.org/10.1101/2020.04.28.20082222,"Risk prediction for poor PPR275525,https://doi.org/10.1101/2021.01.28.21250680,"Changes in symptomatology, re-infection and transmissibility associated with SARS-CoV-2 variant B.1.1.7: an ecological study","Graham MS, Sudre CH, May A, Antonelli M, Murray B, Varsavsky T, Kläser K, Canas LS, Molteni E, Modat M, Drew DA, Nguyen LH, Polidori L, Selvachandran S, Hu C, Capdevila J, Hammers A, Chan AT, Wolf J, Spector TD, Steves CJ, Ourselin S, The COVID-19 Genomics UK (COG-UK) consortium.",,No Journal Info,2021,2021-01-29,Y,,,,"

Background

SARS-CoV-2 variant B.1.1.7 was first identified in December 2020 in England. It is not known if the new variant presents with variation in symptoms or disease course, if previously infected individuals may become reinfected with the new variant, or how the variant’s increased transmissibility affects measures to reduce its spread.

Methods

Using longitudinal symptom reports from 36,920 users of the COVID Symptom Study app testing positive for Covid-19 between 28 September and 27 December 2020, we performed an ecological study to examine the association between the regional proportion of B.1.1.7 and reported symptoms, disease course, rates of reinfection, and transmissibility.

Findings

We found no evidence for changes in reported symptoms or disease duration associated with B.1.1.7. We found a likely reinfection rate of 0.7% (95% CI 0.6-0.8), but no evidence that this was higher compared to older strains. We found an increase in R(t) by a factor of 1.35 (95% CI 1.02-1.69). Despite this, we found that R(t) fell below 1 during regional and national lockdowns, even in regions with high proportions of B.1.1.7.

Interpretation

The lack of change in symptoms indicates existing testing and surveillance infrastructure do not need to change specifically for the new variant, and the reinfection findings suggest that vaccines are likely to remain effective against the new variant.

Funding

Zoe Global Limited, Department of Health, Wellcome Trust, EPSRC, NIHR, MRC, Alzheimer’s Society.

Research in context

Evidence before this study

To identify existing evidence on SARS-CoV-2 variant B.1.1.7 we searched PubMed and Google Scholar for articles between 1 December 2020 and 1 February 2021 using the keywords Covid-19 AND B.1.1.7, finding 281 results. We did not find any studies that investigated B.1.1.7-associated changes in the symptoms experienced, their severity and duration, but found one study showing B.1.1.7 did not change the ratio of symptomatic to asymptomatic infections. We found six articles describing laboratory-based investigations of the responses of B.1.1.7 to vaccine-induced immunity to B.1.1.7, but no work investigating what this means for natural immunity and the likelihood of reinfection outside of the lab. We found five articles demonstrating the increased transmissibility of B.1.1.7.

Added value of this study

To our knowledge, this is the first study to explore changes in symptom type and duration, as well as community reinfection rates, associated with B.1.1.7. The work uses self-reported symptom logs from 36,920 users of the COVID Symptom Study app reporting positive test results between 28 September and 27 December 2020. We find that B.1.1.7 is not associated with changes in the symptoms experienced in Covid-19, nor their duration. Building on existing lab studies, our work suggests that natural immunity developed from previous infection provides similar levels of protection to B.1.1.7. We add to the emerging consensus that B.1.1.7 exhibits increased transmissibility.

Implications of all the available evidence

Our findings suggest that existing criteria for obtaining a Covid-19 test in the community need not change for the rise of B.1.1.7. The fact that immunity developed from infection by wild type variants protects against B.1.1.7 provides an indication that vaccines will remain effective against B.1.1.7. R(t) fell below 1 during the UK’s national lockdown, even in regions with high levels of B.1.1.7, but further investigation is required to establish the factors that enabled this, to facilitate countries seeking to control the spread of B.1.1.7.",,doi:https://doi.org/10.1101/2021.01.28.21250680; html:https://europepmc.org/article/PPR/PPR275525; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR275525&type=FILE&fileName=EMS115539-pdf.pdf&mimeType=application/pdf; pdf:http://pure-oai.bham.ac.uk/ws/files/134813250/1_s2.0_S2468266721000554_main.pdf PPR289287,https://doi.org/10.2139/ssrn.3786058,Inpatient COVID-19 Mortality Has Reduced Over Time: Results from an Observational Cohort,"Bechman K, Yates M, Mann K, Nagra D, Smith L, Rutherford AI, Periselneris J, Walder D, Dobson RJ, Kraljevic Z, Teo JT, Bernal W, Barker RD, Galloway J, Norton S.",,No Journal Info,2021,2021-02-15,N,,,,"Introduction: The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes were different in the first and second waves.

Methods: The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and January 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.

Findings: There were 3,457 COVID-19 admissions, 2,494 hospital discharges and 619 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (25.7% versus 13.2%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.41(0.30, 0.56)p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 1.22(95%CI 0.91, 1.62),p=0.18] or dexamethasone [HR 1.31(95%CI 0.80, 2.14),p=0.29].

Interpretation: There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.

Funding: None.

Conflict of Interest: None declared by authors.

Ethical Approval: This project operated under London South East Research Ethics Committee (reference 18/LO/2048) approval granted to the King’s Electronic Records Research Interface (KERRI); specific work on COVID-19 research was reviewed with expert patient input on a virtual committee with Caldicott Guardian oversight.",,doi:https://doi.org/10.2139/ssrn.3786058; html:https://europepmc.org/article/PPR/PPR289287; doi:https://doi.org/10.2139/ssrn.3786058 PPR290155,https://doi.org/10.1101/2021.02.25.21252402,Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake,"Nguyen LH, Joshi AD, Drew DA, Merino J, Ma W, Lo C, Kwon S, Wang K, Graham MS, Polidori L, Menni C, Sudre CH, Anyane-Yeboa A, Astley CM, Warner ET, Hu CY, Selvachandran S, Davies R, Nash D, Franks PW, Wolf J, Ourselin S, Steves CJ, Spector TD, Chan AT.",,No Journal Info,2021,2021-02-28,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

COVID-19 vaccine hesitancy was greater among racial and ethnic minorities, and Black participants living in the U.S. were less likely to receive a vaccine than White participants. Lower uptake among Black participants in the U.S. during the initial vaccine rollout is attributable to both hesitancy and disparities in access.",,doi:https://doi.org/10.1101/2021.02.25.21252402; html:https://europepmc.org/article/PPR/PPR290155; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR290155&type=FILE&fileName=EMS117911-pdf.pdf&mimeType=application/pdf; pdf:https://www.nature.com/articles/s41467-022-28200-3.pdf -PPR624483,https://doi.org/10.1101/2023.03.02.23286669,Use of a digital application to enhance communication and triage between care homes and National Health Service community services in the United Kingdom: a qualitative evaluation,"Russell S, Stocker R, Cockshott Z, Mason S, Knight J, Hanratty B, Preston N.",,No Journal Info,2023,2023-03-02,N,,,,"Recent years have seen a rise in digital interventions to improve coordination between care homes and NHS services, supporting remote sharing of data on the health of care home residents. Such interventions were key components in the response to the COVID-19 pandemic. This paper presents findings from the qualitative component of an evaluation of an implementation of the HealthCall Digital Care Homes application, across sites in northern England. The implementation commenced prior to the pandemic and continued throughout. Semi-structured, qualitative interviews were held with stakeholders. Interviews were conducted remotely (October 2020 -June 2021). Data were analysed via a reflexive thematic analysis then mapped against Normalization Process Theory (NPT) constructs (coherence, collective action, cognitive participation, and reflexive monitoring) providing a framework to assess implementation success. Thirty-five participants were recruited: 16 care home staff, six NHS community nurses, five relatives of care home residents, four HealthCall team members, three care home residents, and one local authority commissioner. Despite facing challenges such as apprehension towards digital technology among care home staff, the application was viewed positively across stakeholder groups. The HealthCall team maintained formal and informal feedback loop with stakeholders. This resulted in revisions to the intervention and implementation. Appropriate training and problem solving from the HealthCall team and buy-in from care home and NHS staff were key to achieving success across NPT constructs. While this implementation appears broadly successful, establishing rapport and maintaining ongoing support requires significant time, financial backing, and the right individuals in place across stakeholder groups to drive implementation and intervention evolution. The digital literacy of care home staff requires encouragement to enhance their readiness for digital interventions. The COVID-19 pandemic has pushed this agenda forward. Problems with stability across the workforce within care homes need to be addressed to avoid skill loss and support embeddedness of digital interventions.

What is known about this topic?

Improving healthcare delivery in UK care homes is a health policy priority. Digital interventions designed to enhance the referral process between care homes and NHS services and improve the healthcare delivery in care homes have become increasingly common in the UK. The HealthCall Digital Care Homes application is one such intervention. These interventions and their implementations require evaluation to ensure that they operate as intended, function coherently and are considered appropriate and legitimate to the care home setting.

What this paper adds?

The HealthCall Digital Care Homes app is a feasible, appropriate and legitimate intervention for referral, triage and health care support for non-urgent health care needs of care home residents. The ongoing involvement of end users in further developing the intervention, and the level of monitoring and support provided by the implementation team appears to be key to the implementation’s success. The digital preparedness of UK care homes is limited. Ensuring that care homes are digitally enabled, with a digitally literate workforce, should be a policy and research priority.",,doi:https://doi.org/10.1101/2023.03.02.23286669; html:https://europepmc.org/article/PPR/PPR624483; doi:https://doi.org/10.1101/2023.03.02.23286669; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/02/2023.03.02.23286669.full.pdf PPR349882,https://doi.org/10.1101/2021.05.28.21257973,CoMix: Changes in social contacts as measured by the contact survey during the COVID-19 pandemic in England between March 2020 and March 2021,"Gimma A, Munday JD, Wong KL, Coletti P, van Zandvoort K, Prem K, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI, CMMID COVID-19 working group.",,No Journal Info,2021,2021-05-30,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

The CoMix survey provides a unique longitudinal data set for a full year since the first lockdown for use in statistical analyses and mathematical modelling of COVID-19 and other diseases. Recorded contacts reduced dramatically compared to pre-pandemic levels, with changes correlated to government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, mean reported contacts only returned to about half of that observed pre-pandemic.",,doi:https://doi.org/10.1101/2021.05.28.21257973; html:https://europepmc.org/article/PPR/PPR349882; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR349882&type=FILE&fileName=EMS126781-pdf.pdf&mimeType=application/pdf -PPR430732,https://doi.org/10.1101/2021.12.08.21267421,"Vaccine hesitancy for COVID-19 explored in a phenomic study of 259 socio-cognitive-behavioural measures in the UK-REACH study of 12,431 UK healthcare workers","McManus IC, Woolf K, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M.",,No Journal Info,2021,2021-12-09,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

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

Funding

UKMRI-MRC and NIHR",,doi:https://doi.org/10.1101/2021.12.08.21267421; html:https://europepmc.org/article/PPR/PPR430732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR430732&type=FILE&fileName=EMS141669-pdf.pdf&mimeType=application/pdf +PPR624483,https://doi.org/10.1101/2023.03.02.23286669,Use of a digital application to enhance communication and triage between care homes and National Health Service community services in the United Kingdom: a qualitative evaluation,"Russell S, Stocker R, Cockshott Z, Mason S, Knight J, Hanratty B, Preston N.",,No Journal Info,2023,2023-03-02,N,,,,"Recent years have seen a rise in digital interventions to improve coordination between care homes and NHS services, supporting remote sharing of data on the health of care home residents. Such interventions were key components in the response to the COVID-19 pandemic. This paper presents findings from the qualitative component of an evaluation of an implementation of the HealthCall Digital Care Homes application, across sites in northern England. The implementation commenced prior to the pandemic and continued throughout. Semi-structured, qualitative interviews were held with stakeholders. Interviews were conducted remotely (October 2020 -June 2021). Data were analysed via a reflexive thematic analysis then mapped against Normalization Process Theory (NPT) constructs (coherence, collective action, cognitive participation, and reflexive monitoring) providing a framework to assess implementation success. Thirty-five participants were recruited: 16 care home staff, six NHS community nurses, five relatives of care home residents, four HealthCall team members, three care home residents, and one local authority commissioner. Despite facing challenges such as apprehension towards digital technology among care home staff, the application was viewed positively across stakeholder groups. The HealthCall team maintained formal and informal feedback loop with stakeholders. This resulted in revisions to the intervention and implementation. Appropriate training and problem solving from the HealthCall team and buy-in from care home and NHS staff were key to achieving success across NPT constructs. While this implementation appears broadly successful, establishing rapport and maintaining ongoing support requires significant time, financial backing, and the right individuals in place across stakeholder groups to drive implementation and intervention evolution. The digital literacy of care home staff requires encouragement to enhance their readiness for digital interventions. The COVID-19 pandemic has pushed this agenda forward. Problems with stability across the workforce within care homes need to be addressed to avoid skill loss and support embeddedness of digital interventions.

What is known about this topic?

Improving healthcare delivery in UK care homes is a health policy priority. Digital interventions designed to enhance the referral process between care homes and NHS services and improve the healthcare delivery in care homes have become increasingly common in the UK. The HealthCall Digital Care Homes application is one such intervention. These interventions and their implementations require evaluation to ensure that they operate as intended, function coherently and are considered appropriate and legitimate to the care home setting.

What this paper adds?

The HealthCall Digital Care Homes app is a feasible, appropriate and legitimate intervention for referral, triage and health care support for non-urgent health care needs of care home residents. The ongoing involvement of end users in further developing the intervention, and the level of monitoring and support provided by the implementation team appears to be key to the implementation’s success. The digital preparedness of UK care homes is limited. Ensuring that care homes are digitally enabled, with a digitally literate workforce, should be a policy and research priority.",,doi:https://doi.org/10.1101/2023.03.02.23286669; html:https://europepmc.org/article/PPR/PPR624483; doi:https://doi.org/10.1101/2023.03.02.23286669; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/02/2023.03.02.23286669.full.pdf PPR114828,https://doi.org/10.1101/2020.02.26.20028167,Estimation of country-level basic reproductive ratios for novel Coronavirus (COVID-19) using synthetic contact matrices,"Hilton J, Keeling MJ.",,No Journal Info,2020,2020-02-27,Y,,,,"The outbreak of novel coronavirus (COVID-19) has the potential for global spread, infecting large numbers in all countries. In this case, estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio ( R 0 ) is determined by both the nature of pathogen and the network of contacts through which the disease can spread - with this network determined by socio-demographics including age-structure and household composition. Here we focus on the age-structured transmission within the population, using data from China to inform age-dependent susceptibility and synthetic age-mixing matrices to inform the contact network. This allows us to determine the country-specific basic reproductive ratio as a multiplicative scaling of the value from China. We predict that R 0 will be highest across Eastern Europe and Japan, and lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly.","This paper aims to estimate country-specific reproductive ratio, which is determined by the nature of the virus and the network of contacts through which teh disease can spread. The authors predict that the reproductive ratio will be highest across Eastern Europe and Japan, and lowest across Africa, Central America and South-Western Asia. This was based on the ratio of children to older adults in each country, as well as the observed frequency of cases in the elderly.",doi:https://doi.org/10.1101/2020.02.26.20028167; html:https://europepmc.org/article/PPR/PPR114828; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR114828&type=FILE&fileName=EMS88861-pdf.pdf&mimeType=application/pdf +PPR430732,https://doi.org/10.1101/2021.12.08.21267421,"Vaccine hesitancy for COVID-19 explored in a phenomic study of 259 socio-cognitive-behavioural measures in the UK-REACH study of 12,431 UK healthcare workers","McManus IC, Woolf K, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M.",,No Journal Info,2021,2021-12-09,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

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

Funding

UKMRI-MRC and NIHR",,doi:https://doi.org/10.1101/2021.12.08.21267421; html:https://europepmc.org/article/PPR/PPR430732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR430732&type=FILE&fileName=EMS141669-pdf.pdf&mimeType=application/pdf PPR112809,https://doi.org/10.1101/2020.02.12.20022426,Effectiveness of interventions targeting air travellers for delaying local outbreaks of SARS-CoV-2,"Clifford S, Pearson CA, Klepac P, Van Zandvoort K, Quilty BJ, Eggo RM, Flasche S, CMMID COVID-19 working group.",,No Journal Info,2020,2020-02-13,Y,,,,"

Background

We evaluated if interventions aimed at air travellers can delay local SARS-CoV-2 community transmission in a previously unaffected country.

Methods

We simulated infected air travellers arriving into countries with no sustained SARS-CoV-2 transmission or other introduction routes from affected regions. We assessed the effectiveness of syndromic screening at departure and/or arrival & traveller sensitisation to the COVID-2019-like symptoms with the aim to trigger rapid self-isolation and reporting on symptom onset to enable contact tracing. We assumed that syndromic screening would reduce the number of infected arrivals and that traveller sensitisation reduces the average number of secondary cases. We use stochastic simulations to account for uncertainty in both arrival and secondary infections rates, and present sensitivity analyses on arrival rates of infected travellers and the effectiveness of traveller sensitisation. We report the median expected delay achievable in each scenario and an inner 50% interval.

Results

Under baseline assumptions, introducing exit and entry screening in combination with traveller sensitisation can delay a local SARS-CoV-2 outbreak by 8 days (50% interval: 3-14 days) when the rate of importation is 1 infected traveller per week at time of introduction. The additional benefit of entry screening is small if exit screening is effective: the combination of only exit screening and traveller sensitisation can delay an outbreak by 7 days (50% interval: 2-13 days). In the absence of screening, with less effective sensitisation, or a higher rate of importation, these delays shrink rapidly to less than 4 days.

Conclusion

Syndromic screening and traveller sensitisation in combination may have marginally delayed SARS-CoV-2 outbreaks in unaffected countries.",Clifford et al. possible interventions for air travellers that may delay the COVID-19 outbreak in the countries that have not yet had it. They have shown that symptom screening at airports and isolation of those with symptoms can support local containment only if the number of infected travellers are low.,doi:https://doi.org/10.1101/2020.02.12.20022426; html:https://europepmc.org/article/PPR/PPR112809; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR112809&type=FILE&fileName=EMS88768-pdf.pdf&mimeType=application/pdf PPR644063,https://doi.org/10.1101/2023.04.06.23288168,Identification of a specific inflammatory protein biosignature in coronary and peripheral blood associated with increased risk of future cardiovascular events,"Proudfoot D, Gigante B, West NE, Hoole SP, Strawbridge RJ, Tremoli E, Baldassarre D, Williams S.",,No Journal Info,2023,2023-04-12,Y,,,,"

Background and rationale

As an adjunct to coronary intervention, the Liquid Biopsy System (LBS, PlaqueTec, UK) enables accurate intracoronary blood sampling as previously documented. Here we investigate variation between local coronary and remote (peripheral) levels of certain proteins and how this might relate to cardiovascular risk assessment.

Methods and Results

Coronary artery blood samples were collected from 12 patients with obstructive coronary plaques before percutaneous coronary intervention (PCI), using the LBS. Peripheral blood samples were also collected, before and after PCI. Protein levels in coronary and peripheral plasma samples were analysed by proximity extension assay (PEA, Olink) and results were compared with blood samples from healthy controls and reference cohorts. Before PCI, 10/12 patients showed elevations in hepatocyte growth factor (HGF), pappalysin-1 (PAPPA) and spondin-1 (SPON1), in some cases >10-fold greater in coronary compared with peripheral samples. Following PCI, involving iatrogenic plaque rupture prior to stenting, peripheral levels of these proteins were elevated to a similar degree as coronary levels. In the other 2 patients, peripheral elevations for HGF, PAPPA and SPON1 (all >90 th centile) were observed prior to PCI. This protein biosignature was absent in healthy controls but was detected in a minority of individuals in reference cohorts and associated with the occurrence of major adverse cardiovascular events (MACE) and mortality.

Conclusions

From investigation of coronary and peripheral blood samples, we identified a molecular signature, which when present in peripheral blood appears to portend worse outcomes. Measurement of these proteins could therefore aid identification of individuals at high risk of cardiovascular events. (see Graphical Abstract in Supplementary Figures)

Graphical Abstract

Translational Perspective

Through sampling of local coronary blood, we discovered a novel protein biosignature consisting of a combination of elevated levels of HGF, PAPPA and SPON1. When this biosignature was assessed in peripheral samples from reference cardiovascular and Covid cohorts they associated with the occurrence of MACE and mortality. The biosignature protein levels correlated with markers of mast cell and neutrophil activity but not with CRP, possibly indicating a specific inflammatory status. Early detection of this protein signal has potential clinical utility to identify specific patients at increased risk of poor outcomes.",,doi:https://doi.org/10.1101/2023.04.06.23288168; html:https://europepmc.org/article/PPR/PPR644063; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR644063&type=FILE&fileName=EMS174291-pdf.pdf&mimeType=application/pdf PPR170310,https://doi.org/10.1101/2020.05.27.20083287,Estimating excess mortality in people with cancer and multimorbidity in the COVID-19 emergency,"Lai AG, Pasea L, Banerjee A, Denaxas S, Katsoulis M, Chang WH, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Hall G, Davie C, Lawler M, Hemingway H.",,No Journal Info,2020,2020-06-01,Y,,,,"

Background:

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

Methods:

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

Results:

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

Conclusion:

We provide the first estimates of potential excess mortality among people with cancer and multimorbidity due to the COVID-19 emergency and demonstrate dramatic changes in cancer services. To better inform prioritization of cancer care and guide policy change, there is an urgent need for weekly data on cause-specific excess mortality, cancer diagnosis and treatment provision and better intelligence on the use of effective treatments for comorbidities.",,doi:https://doi.org/10.1101/2020.05.27.20083287; html:https://europepmc.org/article/PPR/PPR170310; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR170310&type=FILE&fileName=EMS91512-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/06/01/2020.05.27.20083287.full.pdf @@ -382,8 +382,8 @@ PPR602769,https://doi.org/10.2139/ssrn.3615999,Diabetes and COVID-19 Related Mor PPR153348,https://doi.org/10.1101/2020.04.18.20064774,"How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020","Clark A, Jit M, Warren-Gash C, Guthrie B, Wang HH, Mercer SW, Sanderson C, McKee M, Troeger C, Ong KI, Checchi F, Perel P, Joseph S, Gibbs HP, Banerjee A, Eggo RM, CMMID COVID-19 working group.",,No Journal Info,2020,2020-04-22,Y,,,,"

Background

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

Methods

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

Results

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

Conclusion

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

Quantifying how many and who is at increased risk of severe COVID-19 illness is critical to help countries design more effective interventions to protect vulnerable individuals and reduce pressure on health systems. This information can also inform a broader assessment of the health, social and economic implications of shielding various groups.","""This paper estimates the likely number of global population that would be at increased risk of severe COVID-19 disease. They estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe.""",doi:https://doi.org/10.1101/2020.04.18.20064774; html:https://europepmc.org/article/PPR/PPR153348; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR153348&type=FILE&fileName=EMS90450-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/04/22/2020.04.18.20064774.full.pdf PPR172592,https://doi.org/10.1101/2020.06.05.20121962,TRACKing Excess Deaths (TRACKED) – an interactive online tool to monitor excess deaths associated with COVID-19 pandemic in the United Kingdom,"Poon MT, Brennan PM, Jin K, Figueroa JD, Sudlow CL.",,No Journal Info,2020,2020-06-07,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

Continuous monitoring of excess mortality trends and further integration of age- and gender-stratified and underlying cause of death data beyond COVID-19 will allow dynamic assessment of the impacts of indirect and direct mortality of the COVID-19 pandemic.",,doi:https://doi.org/10.1101/2020.06.05.20121962; html:https://europepmc.org/article/PPR/PPR172592; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR172592&type=FILE&fileName=EMS91985-pdf.pdf&mimeType=application/pdf PPR308156,https://doi.org/10.1101/2021.04.02.21254818,Covid-19 does not look like what you are looking for: Clustering symptoms by nation and multi-morbidities reveal substantial differences to the classical symptom triad,"Kadirvelu B, Burcea G, Quint JK, Costelloe CE, Faisal AA.",,No Journal Info,2021,2021-04-07,Y,,,,"

ABSTRACT

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

Executive Summary

Evidence before this work

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

Added value of this work

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

Implications of the evidence

These factors, uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk.",,doi:https://doi.org/10.1101/2021.04.02.21254818; html:https://europepmc.org/article/PPR/PPR308156; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR308156&type=FILE&fileName=EMS121846-pdf.pdf&mimeType=application/pdf -PPR518927,https://doi.org/10.1101/2022.07.14.22277638,Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: Findings from a Mendelian randomisation study,"Hamilton F, Thomas M, Arnold D, Palmer T, Moran E, Mentzer AJ, Maskell N, Baillie K, Summers C, Hingorani A, MacGowan A, Khandakar GM, Mitchell R, Smith GD, Ghazal P, Timpson NJ.",,No Journal Info,2022,2022-07-15,Y,,,,"

Introduction

Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin-6 (IL-6). Genetic variants in IL6R known to downregulate IL-6 signalling are associated with improved COVID-19 outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RA). We hypothesised that blockade of IL6R could also improve outcomes in sepsis.

Methods

We performed a Mendelian randomisation analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis, sepsis severity, other infections, and COVID-19. We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP in a similar analysis.

Results

In the UK Biobank cohort (N=485,825, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of sepsis (OR=0.80; 95% CI 0.66-0.96, per unit of natural log transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR=0.74; 95% CI 0.38-0.70); critical care admission with sepsis (OR=0.48, 95% CI 0.30-0.78) and critical care death with sepsis (OR=0.37, 95% CI 0.14 - 0.98) Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 - 0.97) and for sepsis survival in critical care (OR=0.22; 95% CI 0.04- 1.31) in the GainS and GenOSept consortium. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR=0.69, 95% 0.57 - 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results.

Conclusions

IL6R blockade is causally associated with reduced incidence of sepsis, sepsis related critical care admission, and sepsis related mortality. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. This data suggests a randomised trial of IL-6 receptor antagonists in sepsis should be considered.",,doi:https://doi.org/10.1101/2022.07.14.22277638; html:https://europepmc.org/article/PPR/PPR518927; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR518927&type=FILE&fileName=EMS150974-pdf.pdf&mimeType=application/pdf PPR384592,https://doi.org/10.1101/2021.08.17.21260846,"COVID-19 Infection, Admission and Death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project","Rutter M, Lanyon PC, Grainge MJ, Hubbard R, Peach E, Bythell M, Stilwell P, Aston J, Stevens S, Pearce FA.",,No Journal Info,2021,2021-08-18,Y,,,,"

Objectives

To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared to the general population.

Methods

We used Hospital Episode Statistics to identify all people alive 01 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths.

Results

We identified a cohort of 168,680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardised infection rate was 1.54 (95% CI 1.50-1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.41 (2.30 – 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population.

Conclusions

During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared to the general population. These increases were seen despite shielding policies.

Key Messages

People with RAIRD were at increased risk of COVID-19 infection during the first wave. Compared to the general population, they had over twice the risk of COVID-19-related death. These increased risks were seen despite shielding policies in place in England.",,doi:https://doi.org/10.1101/2021.08.17.21260846; html:https://europepmc.org/article/PPR/PPR384592; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR384592&type=FILE&fileName=EMS133258-pdf.pdf&mimeType=application/pdf +PPR518927,https://doi.org/10.1101/2022.07.14.22277638,Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: Findings from a Mendelian randomisation study,"Hamilton F, Thomas M, Arnold D, Palmer T, Moran E, Mentzer AJ, Maskell N, Baillie K, Summers C, Hingorani A, MacGowan A, Khandakar GM, Mitchell R, Smith GD, Ghazal P, Timpson NJ.",,No Journal Info,2022,2022-07-15,Y,,,,"

Introduction

Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin-6 (IL-6). Genetic variants in IL6R known to downregulate IL-6 signalling are associated with improved COVID-19 outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RA). We hypothesised that blockade of IL6R could also improve outcomes in sepsis.

Methods

We performed a Mendelian randomisation analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis, sepsis severity, other infections, and COVID-19. We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP in a similar analysis.

Results

In the UK Biobank cohort (N=485,825, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of sepsis (OR=0.80; 95% CI 0.66-0.96, per unit of natural log transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR=0.74; 95% CI 0.38-0.70); critical care admission with sepsis (OR=0.48, 95% CI 0.30-0.78) and critical care death with sepsis (OR=0.37, 95% CI 0.14 - 0.98) Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 - 0.97) and for sepsis survival in critical care (OR=0.22; 95% CI 0.04- 1.31) in the GainS and GenOSept consortium. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR=0.69, 95% 0.57 - 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results.

Conclusions

IL6R blockade is causally associated with reduced incidence of sepsis, sepsis related critical care admission, and sepsis related mortality. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. This data suggests a randomised trial of IL-6 receptor antagonists in sepsis should be considered.",,doi:https://doi.org/10.1101/2022.07.14.22277638; html:https://europepmc.org/article/PPR/PPR518927; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR518927&type=FILE&fileName=EMS150974-pdf.pdf&mimeType=application/pdf PPR263081,https://doi.org/10.1101/2021.01.06.21249352,OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19,"The OpenSAFELY Collaborative, Curtis HJ, MacKenna B, MacKenna B, Croker R, Inglesby P, Walker AJ, Morley J, Mehrkar A, Morton CE, Bacon S, Hickman G, Bates C, Morley J, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-01-08,Y,,,,"

Background

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

Objective

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

Methods

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

Results

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

Conclusions

We successfully delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September 2020, with some important tests less affected. Records of respiratory infections decreased with the exception of codes related to COVID-19, whilst activity of other respiratory disease codes was mixed. We are expanding the NHS Service Restoration Observatory in collaboration with clinicians, commissioners and researchers and welcome feedback.",,doi:https://doi.org/10.1101/2021.01.06.21249352; html:https://europepmc.org/article/PPR/PPR263081; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR263081&type=FILE&fileName=EMS110198-pdf.pdf&mimeType=application/pdf PPR187554,https://doi.org/10.1101/2020.07.14.20152629,COVID-19 infection and attributable mortality in UK care homes: Cohort study using active surveillance and electronic records (March-June 2020),"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hemingway H, Hayward A, Shallcross L.",,No Journal Info,2020,2020-07-15,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

Findingss:

uggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,doi:https://doi.org/10.1101/2020.07.14.20152629; html:https://europepmc.org/article/PPR/PPR187554; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR187554&type=FILE&fileName=EMS87167-pdf.pdf&mimeType=application/pdf; pdf:https://discovery.ucl.ac.uk/10122604/10/Dutey-Magni_afab060.pdf PPR232332,https://doi.org/10.1101/2020.10.29.20222174,COVID-19 collateral: Indirect acute effects of the pandemic on physical and mental health in the UK,"Mansfield KE, Mathur R, Tazare J, Henderson AD, Mulick A, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Cook S, Wong AY, Strongman H, Wing K, Warren-Gash C, Cadogan SL, Smeeth L, Hayes JF, Quint JK, McKee M, M Langan S.",,No Journal Info,2020,2020-10-30,Y,,,,"

ABSTRACT

Background

Concerns have been raised that the response to the UK COVID-19 pandemic may have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We asked what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic?

Methods

Using electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (2017-2020), we calculated weekly primary care contacts for selected acute physical and mental health conditions (including: anxiety, depression, acute alcohol-related events, asthma and chronic obstructive pulmonary disease [COPD] exacerbations, cardiovascular and diabetic emergencies). We used interrupted time series (ITS) analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (‘lockdown’) compared to the period prior to their introduction in March 2020.

Findings

The overall population included 9,863,903 individuals on 1 st January 2017. Primary care contacts for all conditions dropped dramatically after introduction of population-wide restrictions. By July 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. The largest reductions were for contacts for: diabetic emergencies (OR: 0.35, 95% CI: 0.25-0.50), depression (OR: 0.53, 95% CI: 0.52-0.53), and self-harm (OR: 0.56, 95% CI: 0.54-0.58).

Interpretation

There were substantial reductions in primary care contacts for acute physical and mental conditions with restrictions, with limited recovery by July 2020. It is likely that much of the deficit in care represents unmet need, with implications for subsequent morbidity and premature mortality. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people experiencing the conditions and healthcare provision. Maintaining access must be a key priority in future public health planning (including further restrictions).

Funding

Wellcome Trust Senior Fellowship (SML), Health Data Research UK.

RESULTS IN CONTEXT

Evidence before this study

A small study in 47 GP practices in a largely deprived, urban area of the UK (Salford) reported that primary care consultations for four broad diagnostic groups (circulatory disease, common mental health problems, type 2 diabetes mellitus and malignant cancer) declined by 16-50% between March and May 2020, compared to what was expected based on data from January 2010 to March 2020. We searched Medline for other relevant evidence of the indirect effect of the COVID-19 pandemic on physical and mental health from inception to September 25 th 2020, for articles published in English, with titles including the search terms (“covid*” or “coronavirus” or “sars-cov-2”), and title or abstracts including the search terms (“indirect impact” or “missed diagnos*” or “missing diagnos*” or “delayed diagnos*” or ((“present*” or “consult*” or “engag*” or “access*”) AND (“reduction” or “decrease” or “decline”)). We found no further studies investigating the change in primary care contacts for specific physical- and mental-health conditions indirectly resulting from the COVID-19 pandemic or its control measures. There has been a reduction in hospital admissions and presentations to accident and emergency departments in the UK, particularly for myocardial infarctions and cerebrovascular accidents. However, there is no published evidence specifically investigating the changes in primary care contacts for severe acute physical and mental health conditions.

Added value of this study

To our knowledge this is the first study to explore changes in healthcare contacts for acute physical and mental health conditions in a large population representative of the UK. We used electronic primary care health records of nearly 10 million individuals across the UK to investigate the indirect impact of COVID-19 on primary care contacts for mental health, acute alcohol-related events, asthma/chronic obstructive pulmonary disease (COPD) exacerbations, and cardiovascular and diabetic emergencies up to July 2020. For all conditions studied, we found primary care contacts dropped dramatically following the introduction of population-wide restriction measures in March 2020. By July 2020, with the exception of unstable angina and acute alcohol-related events, primary care contacts for all conditions studied had not recovered to pre-lockdown levels. In the general population, estimates of the absolute reduction in the number of primary care contacts up to July 2020, compared to what we would expect from previous years varied from fewer than 10 contacts per million for some cardiovascular outcomes, to 12,800 per million for depression and 6,600 for anxiety. In people with COPD, we estimated there were 43,900 per million fewer contacts for COPD exacerbations up to July 2020 than what we would expect from previous years.

Implicatins of all the available evidence

While our results may represent some genuine reduction in disease frequency (e.g. the restriction measures may have improved diabetic glycaemic control due to more regular daily routines at home), it is more likely the reduced primary care conatcts we saw represent a substantial burden of unmet need (particularly for mental health conditions) that may be reflected in subsequent increased mortality and morbidity. Health service providers should take steps to prepare for increased demand in the coming months and years due to the short and longterm ramifications of reduced access to care for severe acute physical and mental health conditions. Maintaining access to primary care is key to future public health planning in relation to the pandemic.",,doi:https://doi.org/10.1101/2020.10.29.20222174; html:https://europepmc.org/article/PPR/PPR232332; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR232332&type=FILE&fileName=EMS102733-pdf.pdf&mimeType=application/pdf @@ -402,11 +402,11 @@ PPR141100,https://doi.org/10.1101/2020.04.05.20054528,"Estimating number of case PPR183540,https://doi.org/10.1101/2020.07.03.20145839,"The Impact of COVID-19 on Adjusted Mortality Risk in Care Homes for Older Adults in Wales, United Kingdom: A retrospective population-based cohort study for mortality in 2016-2020","Hollinghurst J, Lyons J, Fry R, Akbari A, Gravenor M, Watkins A, Verity F, Lyons RA.",,No Journal Info,2020,2020-07-04,Y,,,,"

ABSTRACT

Background

Mortality in care homes has had a prominent focus during the COVID-19 outbreak. Multiple and interconnected challenges face the care home sector in the prevention and management of outbreaks of COVID-19, including adequate supply of personal protective equipment, staff shortages, and insufficient or lack of timely COVID-19 testing. Care homes are particularly vulnerable to infectious diseases.

Aim

To analyse the mortality of older care home residents in Wales during COVID-19 lockdown and compare this across the population of Wales and the previous 4-years.

Study Design and Setting

We used anonymised Electronic Health Records (EHRs) and administrative data from the Secure Anonymised Information Linkage (SAIL) Databank to create a cross-sectional cohort study. We anonymously linked data for Welsh residents to mortality data up to the 14 th June 2020.

Methods

We calculated survival curves and adjusted Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of mortality. We adjusted hazard ratios for age, gender, social economic status and prior health conditions.

Results

Survival curves show an increased proportion of deaths between 23 rd March and 14 th June 2020 in care homes for older people, with an adjusted HR of 1·72 (1·55, 1·90) compared to 2016. Compared to the general population in 2016-2019, adjusted care home mortality HRs for older adults rose from 2·15 (2·11,2·20) in 2016-2019 to 2·94 (2·81,3·08) in 2020.

Conclusions

The survival curves and increased HRs show a significantly increased risk of death in the 2020 study periods.",,doi:https://doi.org/10.1101/2020.07.03.20145839; html:https://europepmc.org/article/PPR/PPR183540; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR183540&type=FILE&fileName=EMS87632-pdf.pdf&mimeType=application/pdf PPR207614,https://doi.org/10.1101/2020.08.25.20181198,The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya,"Mburu C, Ojal J, Chebet R, Akech D, Karia B, Tuju J, Sigilai A, Abbas K, Jit M, Funk S, Smits G, van Gageldonk P, van der Klis F, Tabu C, Nokes D, Scott J, Flasche S, Adetifa I, LSHTM CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-08-31,N,,,,"

Background

The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.

Methods

Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.

Findings

In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 22% (0-46). As the COVID-19 restrictions to physical contact are lifted, from December 2020, the probability of a large measles outbreak increased to 31% (8-51), 35% (16-52) and 43% (31-56) assuming a 15%, 50% and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 37% (17-54), 44% (29-57) and 57% (48-65) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of restrictions on contact can be overcome by conducting an SIA with ≥ 95% coverage in under-fives.

Interpretation

While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once physical distancing is relaxed. Implementing delayed SIAs will be critical for prevention of measles outbreaks once contact restrictions are fully lifted in Kenya.

Funding

The United Kingdom’s Medical Research Council and the Department for International Development",,doi:https://doi.org/10.1101/2020.08.25.20181198; html:https://europepmc.org/article/PPR/PPR207614; doi:https://doi.org/10.1101/2020.08.25.20181198; pdf:https://europepmc.org/articles/pmc7854026?pdf=render PPR254227,https://doi.org/10.1101/2020.12.14.20248155,Investigating mental and physical disorders associated with COVID-19 in online health forums,"Patel R, Smeraldi F, Abdollahyan M, Irving J, Bessant C.",,No Journal Info,2020,2020-12-16,Y,,,,"

Objectives:

Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users. Setting and design: We obtained data from 739,434 posts by 53,134 unique users of three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1st January 2020 to 31st May 2020. Using NLP, we analysed the content of posts related to COVID-19. Primary outcome measures: (i) Proportion of forum posts containing COVID-19 keywords (ii) Proportion of forum users making their very first post about COVID-19 (iii) Number of COVID-19 related posts containing content related to physical and mental health comorbidities Results: Posts discussing COVID-19 and related comorbid disorders spiked in early- to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health.

Conclusions:

We demonstrate it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.",,doi:https://doi.org/10.1101/2020.12.14.20248155; html:https://europepmc.org/article/PPR/PPR254227; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR254227&type=FILE&fileName=EMS108690-pdf.pdf&mimeType=application/pdf -PPR568016,https://doi.org/10.1101/2022.11.06.22281986,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,No Journal Info,2022,2022-11-07,Y,,,,"

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27 th August 2020 to 11 th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564, derivation 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.

What is already known on this subject

Uneven vaccination in low- and middle-income countries (LMICs) coupled with less resilient health care provision mean that emergency health care systems in LMICs may still be at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-stratification scores may help rapidly triage need for hospitalisation. However, those proposed for use in the ED for patients with suspected COVID-19 have been developed and validated in high-income settings.

What this study adds

The LMIC-PRIEST score has been robustly developed using a large routine dataset from the Western Cape, South Africa and is directly applicable to existing triage practices in LMICs. External validation across both income settings and COVID-19 variants showed good discrimination and high sensitivity (at lower thresholds) to a composite outcome indicating need for inpatient admission from the ED

How this study might affect research, practice or policy

Use of the LMIC-PRIEST score at thresholds of three or less would allow identification of very low-risk patients (negative predictive value ≥0.99) across all settings assessed During periods of increased demand, this could allow the rapid identification and discharge of patients from the ED using information collected at initial assessment.",,doi:https://doi.org/10.1101/2022.11.06.22281986; html:https://europepmc.org/article/PPR/PPR568016; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR568016&type=FILE&fileName=EMS156830-pdf.pdf&mimeType=application/pdf PPR250078,https://doi.org/10.1101/2020.12.03.20242941,Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values,"Cavallaro M, Moiz H, Keeling MJ, McCarthy ND.",,No Journal Info,2020,2020-12-07,Y,,,,"Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.

Author summary

The design is a retrospective cohort study of 13954 in-patients of ages ranging from 1 to 105 year (IQR: 56, 70, 81) with a confirmed diagnosis of COVID-19 by 28th June 2020. This study used multivariable logistic regression to generate odd ratios (ORs) multiply adjusted for 37 covariates (comorbidities, demographic, and others) selected on the basis of clinical interest and prior findings. Results were supplemented by gradient-boosted decision tree (GBDT) classification to generate Shapley values in order to evaluate the impact of the covariates on model output for all patients. Factors are differentially associated with death and ICUA and among patients. Deaths due to COVID-19 were associated with immunosuppression due to disease (OR 1.39, 95% CI 1.10-1.76), type-2 diabetes (OR 1.31, 95% CI 1.17-1.46), chronic respiratory disease (OR 1.19, 95% CI 1.05-1.35), age (OR 1.56/10-year increment, 95% CI 1.52-1.61), and male sex (OR 1.54, 95% CI1.42-1.68). Associations of ICUA with some factors differed in direction (e.g., age, chronic respiratory disease). Self-reported ethnicities were strongly but variably associated with both outcomes. GBDTs had similar performance (ROC-AUC, ICUA 0.83, death 0.68 for GBDT; 0.80 and 0.68 for logistic regression). We derived importance scores based on Shapley values which were consistent with the ORs, despite the underlying machine-learning model being intrinsically different to the logistic regression. Chronic heart disease, hypertension, other comorbidities, and some ethnicities had Shapley impacts on death ranging from positive to negative among different patients, although consistently associated with ICUA for all. Immunosuppressive disease, type-2 diabetes, and chronic liver and respiratory diseases had positive impacts on death with either positive or negative on ICUA. We highlight the complexity of informing clinical practice and public-health interventions. We recommend that clinical support systems should not only predict patients at risk, but also yield interpretable outputs for validation by domain experts.",,doi:https://doi.org/10.1101/2020.12.03.20242941; html:https://europepmc.org/article/PPR/PPR250078; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR250078&type=FILE&fileName=EMS108093-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/29/2020.12.03.20242941.full.pdf +PPR568016,https://doi.org/10.1101/2022.11.06.22281986,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,No Journal Info,2022,2022-11-07,Y,,,,"

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27 th August 2020 to 11 th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564, derivation 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.

What is already known on this subject

Uneven vaccination in low- and middle-income countries (LMICs) coupled with less resilient health care provision mean that emergency health care systems in LMICs may still be at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-stratification scores may help rapidly triage need for hospitalisation. However, those proposed for use in the ED for patients with suspected COVID-19 have been developed and validated in high-income settings.

What this study adds

The LMIC-PRIEST score has been robustly developed using a large routine dataset from the Western Cape, South Africa and is directly applicable to existing triage practices in LMICs. External validation across both income settings and COVID-19 variants showed good discrimination and high sensitivity (at lower thresholds) to a composite outcome indicating need for inpatient admission from the ED

How this study might affect research, practice or policy

Use of the LMIC-PRIEST score at thresholds of three or less would allow identification of very low-risk patients (negative predictive value ≥0.99) across all settings assessed During periods of increased demand, this could allow the rapid identification and discharge of patients from the ED using information collected at initial assessment.",,doi:https://doi.org/10.1101/2022.11.06.22281986; html:https://europepmc.org/article/PPR/PPR568016; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR568016&type=FILE&fileName=EMS156830-pdf.pdf&mimeType=application/pdf PPR227658,https://doi.org/10.1101/2020.10.18.20214585,Exploring surveillance data biases when estimating the reproduction number: with insights into subpopulation transmission of Covid-19 in England,"Sherratt K, Abbott S, Meakin SR, Hellewell J, Munday JD, Bosse N, Jit M, Funk S, CMMID Covid-19 working group.",,No Journal Info,2020,2020-10-20,Y,,,,"The time-varying reproduction number ( R t the average number secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of R t estimates to different data sources representing Covid-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions, and deaths with confirmed Covid-19 in seven regions of England over March through August 2020. We estimated R t using a model that mapped unobserved infections to each data source. We then compared differences in R t with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. R t estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test-positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of disease. We highlight that policy makers could better target interventions by considering the source populations of R t estimates. Further work should clarify the best way to combine and interpret R t estimates from different data sources based on the desired use.",,doi:https://doi.org/10.1101/2020.10.18.20214585; html:https://europepmc.org/article/PPR/PPR227658; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR227658&type=FILE&fileName=EMS98719-pdf.pdf&mimeType=application/pdf -PPR501803,https://doi.org/10.1101/2022.06.01.22275674,OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care activity across six clinical areas during the COVID-19 pandemic,"Curtis HJ, MacKenna B, Wiedemann M, Fisher L, Croker R, Morton CE, Inglesby P, Walker AJ, Morley J, Mehrkar A, Bacon SC, Hickman G, Evans D, Ward T, Davy S, Hulme WJ, Macdonald O, Conibere R, Lewis T, Myers M, Wanninayake S, Collison K, Drury C, Samuel M, Sood H, Cipriani A, Fazel S, Sharma M, Baqir W, Bates C, Parry J, Goldacre B.",,No Journal Info,2022,2022-06-02,Y,,,,"

Background

The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible.

Aims

Using routinely collected data, our aim was to describe changes in the volume and variation of coded clinical activity in general practice in: (i) cardiovascular disease, (ii) diabetes, (iii) mental health, (iv) female and reproductive health, (v) screening, and (vi) processes related to medication.

Design and setting

With the approval of NHS England, we conducted a cohort study of 23.8 million patient records in general practice, in-situ using OpenSAFELY.

Methods

We selected common primary care activity using CTV3 codes and keyword searches from January 2019 - December 2020, presenting median and deciles of code usage across practices per month.

Results

We identified substantial and widespread changes in clinical activity in primary care since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health, e.g. “Depression interim review” (median across practices in December 2020 -41.6% compared to December 2019).

Conclusions

Granular NHS GP data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for key measures identified here as well as further studies, using primary care data to monitor and mitigate the indirect health impacts of Covid-19 on the NHS.

How this fits in

During the COVID-19 pandemic, routine healthcare services in England faced significant disruption, and NHS England recommended restoring NHS services to near-normal levels before winter 2020. Our previous report covered the disruption and recovery in pathology tests and respiratory activity: here we describe an additional six areas of common primary care activity. We found most activities exhibited significant reductions during pandemic wave 1 (with most recovering to near-normal levels by December); however many important aspects of care - especially those of a more time-critical nature - were maintained throughout the pandemic. We recommend key measures for ongoing monitoring and further investigation of the impacts on health inequalities, to help measure and mitigate the ongoing indirect health impacts of COVID-19 on the NHS.",,doi:https://doi.org/10.1101/2022.06.01.22275674; html:https://europepmc.org/article/PPR/PPR501803; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR501803&type=FILE&fileName=EMS145734-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/02/2022.06.01.22275674.full.pdf PPR264211,https://doi.org/10.1101/2021.01.11.21249461,A national retrospective cohort study of mechanical ventilator availability and its association with mortality risk in intensive care patients with COVID-19,"Wilde H, Mellan TA, Hawryluk I, Dennis J, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer S.",,No Journal Info,2021,2021-01-13,Y,,,,"

Objectives:

To determine if there is an association between survival rates in intensive care units (ICU) and occupancy of the unit on the day of admission.

Design:

National retrospective observational cohort study during the COVID-19 pandemic.

Setting:

90 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Participants: 6,686 adults admitted to an ICU in England between 2nd April and 1st December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. Interventions: N/A Main Outcomes and Measures: A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible) bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).

Results:

121,151 patient-days were observed, with a mortality rate of 20.8 per 1,000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (>85% occupancy versus the baseline of 45 to 85%) [OR 1.18 (95% posterior credible interval (PCI): 1.00 to 1.38)]. In contrast, mortality was decreased for admissions during periods of low occupancy (<45% relative to the baseline) [OR 0.79 (95% PCI: 0.69 to 0.90)]. Conclusion and Relevance: Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Public health interventions (such as expeditious vaccination programmes and non-pharmaceutical interventions) to control both incidence and prevalence of COVID-19, and therefore keep ICU occupancy low in the context of the pandemic, are necessary to mitigate the impact of this type of resource saturation. Trial Registration: N/A",,doi:https://doi.org/10.1101/2021.01.11.21249461; html:https://europepmc.org/article/PPR/PPR264211; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR264211&type=FILE&fileName=EMS110554-pdf.pdf&mimeType=application/pdf +PPR501803,https://doi.org/10.1101/2022.06.01.22275674,OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care activity across six clinical areas during the COVID-19 pandemic,"Curtis HJ, MacKenna B, Wiedemann M, Fisher L, Croker R, Morton CE, Inglesby P, Walker AJ, Morley J, Mehrkar A, Bacon SC, Hickman G, Evans D, Ward T, Davy S, Hulme WJ, Macdonald O, Conibere R, Lewis T, Myers M, Wanninayake S, Collison K, Drury C, Samuel M, Sood H, Cipriani A, Fazel S, Sharma M, Baqir W, Bates C, Parry J, Goldacre B.",,No Journal Info,2022,2022-06-02,Y,,,,"

Background

The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible.

Aims

Using routinely collected data, our aim was to describe changes in the volume and variation of coded clinical activity in general practice in: (i) cardiovascular disease, (ii) diabetes, (iii) mental health, (iv) female and reproductive health, (v) screening, and (vi) processes related to medication.

Design and setting

With the approval of NHS England, we conducted a cohort study of 23.8 million patient records in general practice, in-situ using OpenSAFELY.

Methods

We selected common primary care activity using CTV3 codes and keyword searches from January 2019 - December 2020, presenting median and deciles of code usage across practices per month.

Results

We identified substantial and widespread changes in clinical activity in primary care since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health, e.g. “Depression interim review” (median across practices in December 2020 -41.6% compared to December 2019).

Conclusions

Granular NHS GP data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for key measures identified here as well as further studies, using primary care data to monitor and mitigate the indirect health impacts of Covid-19 on the NHS.

How this fits in

During the COVID-19 pandemic, routine healthcare services in England faced significant disruption, and NHS England recommended restoring NHS services to near-normal levels before winter 2020. Our previous report covered the disruption and recovery in pathology tests and respiratory activity: here we describe an additional six areas of common primary care activity. We found most activities exhibited significant reductions during pandemic wave 1 (with most recovering to near-normal levels by December); however many important aspects of care - especially those of a more time-critical nature - were maintained throughout the pandemic. We recommend key measures for ongoing monitoring and further investigation of the impacts on health inequalities, to help measure and mitigate the ongoing indirect health impacts of COVID-19 on the NHS.",,doi:https://doi.org/10.1101/2022.06.01.22275674; html:https://europepmc.org/article/PPR/PPR501803; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR501803&type=FILE&fileName=EMS145734-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/02/2022.06.01.22275674.full.pdf PPR509645,https://doi.org/10.1101/2022.06.23.22276802,OpenSAFELY: Representativeness of Electronic Health Record platform OpenSAFELY-TPP data compared to the population of England,"Andrews CD, Schultze A, Curtis HJ, Hulme WJ, Tazare J, Evans SJ, Mehrkhar A, Bacon S, Hickman G, Bates C, Parry J, Hester F, Harper S, Cockburn J, Evans D, Ward T, Davey S, Inglesby P, Goldacre B, MacKenna B, Tomlinson L, Walker AJ.",,No Journal Info,2022,2022-06-23,Y,,,,"

Background

Since its inception in March 2020, data from the OpenSAFELY-TPP electronic health record platform has been used for more than 50 studies relating to the global COVID-19 emergency. OpenSAFELY-TPP data is derived from practices in England using SystmOne software, and has been used for the majority of these studies. We set out to investigate the representativeness of OpenSAFELY-TPP data by comparing it to national population estimates.

Methods

With the approval of NHS England, we describe the age, sex, Index of Multiple Deprivation and ethnicity of the OpenSAFELY-TPP population compared to national estimates from the Office for National Statistics. The five leading causes of death occurring between the 1st January 2020 and the 31st December 2020 were also compared to deaths registered in England during the same period.

Results

Despite regional variations, TPP is largely representative of the general population of England in terms of IMD (all within 1.1 percentage points), age, sex (within 0.1 percentage points), ethnicity and causes of death. The proportion of the five leading causes of death is broadly similar to those reported by ONS (all within 1 percentage point).

Conclusions

Data made available via OpenSAFELY-TPP is broadly representative of the English population.

Summary

Users of OpenSAFELY must consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. Although the coverage of TPP practices varies regionally across England, TPP registered patients are generally representative of the English population as a whole in terms of key demographic characteristics.

Key messages

There is regional variability across England in terms of key population characteristics Users of OpenSAFELY should carefully consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. TPP registered patients are a representative sub-sample of the English population as a whole in terms of age, sex, IMD and ethnicity. The proportions of the five leading causes of death in TPP in 2020 are broadly similar to those reported by ONS.",,doi:https://doi.org/10.1101/2022.06.23.22276802; html:https://europepmc.org/article/PPR/PPR509645; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR509645&type=FILE&fileName=EMS146338-pdf.pdf&mimeType=application/pdf PPR167046,https://doi.org/10.1101/2020.05.19.20106641,Study Data Element Mapping: Feasibility of Defining Common Data Elements Across COVID-19 Studies,"Mathewson P, Gordon B, Snowley K, Fennessy C, Denniston A, Sebire N.",,No Journal Info,2020,2020-05-26,N,,,,"

Background:

Numerous clinical studies are now underway investigating aspects of COVID-19. The aim of this study was to identify a selection of national and/or multicentre clinical COVID-19 studies in the United Kingdom to examine the feasibility and outcomes of documenting the most frequent data elements common across studies to rapidly inform future study design and demonstrate proof-of-concept for further subject-specific study data element mapping to improve research data management.

Methods:

25 COVID-19 studies were included. For each, information regarding the specific data elements being collected was recorded. Data elements collated were arbitrarily divided into categories for ease of visualisation. Elements which were most frequently and consistently recorded across studies are presented in relation to their relative commonality.

Results:

Across the 25 studies, 261 data elements were recorded in total. The most frequently recorded 100 data elements were identified across all studies and are presented with relative frequencies. Categories with the largest numbers of common elements included demographics, admission criteria, medical history and investigations. Mortality and need for specific respiratory support were the most common outcome measures, but with specific studies including a range of other outcome measures.

Conclusion:

The findings of this study have demonstrated that it is feasible to collate specific data elements recorded across a range of studies investigating a specific clinical condition in order to identify those elements which are most common among studies. These data may be of value for those establishing new studies and to allow researchers to rapidly identify studies collecting data of potential use hence minimising duplication and increasing data re-use and interoperability",,doi:https://doi.org/10.1101/2020.05.19.20106641; html:https://europepmc.org/article/PPR/PPR167046; doi:https://doi.org/10.1101/2020.05.19.20106641; pdf:https://discovery.ucl.ac.uk/10108130/1/2020.05.19.20106641v1.full.pdf PPR230607,https://doi.org/10.1101/2020.10.26.20219576,Impact of the COVID-19 pandemic on remote mental healthcare and prescribing in psychiatry,"Patel R, Irving J, Brinn A, Broadbent M, Shetty H, Pritchard M, Downs J, Stewart R, Harland R, McGuire P.",,No Journal Info,2020,2020-10-27,Y,,,,"

Objectives

The recent COVID-19 pandemic has disrupted mental healthcare delivery, with many services shifting from in- person to remote patient contact. We investigated the impact of the pandemic on the use of remote consultation and on the prescribing of psychiatric medications.

Design and setting

The Clinical Record Interactive Search tool (CRIS) was used to examine de-identified electronic health records (EHRs) of people receiving mental healthcare from the South London and Maudsley (SLaM) NHS Foundation Trust. Data from the period before and after the onset of the pandemic were analysed using linear regression, and visualised using locally estimated scatterplot smoothing (LOESS).

Participants

All patients receiving care from SLaM between 7 th January 2019 and 20 th September 2020 (around 37,500 patients per week).

Outcome measures

The number of clinical contacts (in-person, remote or non-attended) with mental healthcare professionals per week Prescribing of antipsychotic and mood stabiliser medications per week

Results

Following the onset of the pandemic, the frequency of in-person contacts was significantly reduced compared to that in the previous year (β coefficient: −5829.6 contacts, 95% CI −6919.5 to −4739.6, p<0.001), while the frequency of remote contacts significantly increased (β coefficient: 3338.5 contacts, 95% CI 3074.4 to 3602.7, p<0.001). Rates of remote consultation were lower in older adults than in working age adults, children and adolescents. Despite this change in the type of patient contact, antipsychotic and mood stabiliser prescribing remained at similar levels.

Conclusions

The COVID-19 pandemic has been associated with a marked increase in remote consultation, particularly among younger patients. However, there was no evidence that this has led to changes in psychiatric prescribing. Nevertheless, further work is needed to ensure that older patients are able to access mental healthcare remotely.",,doi:https://doi.org/10.1101/2020.10.26.20219576; html:https://europepmc.org/article/PPR/PPR230607; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR230607&type=FILE&fileName=EMS101579-pdf.pdf&mimeType=application/pdf diff --git a/data/covid/papers.csv b/data/covid/papers.csv index 72dd36fb..8cbc550f 100644 --- a/data/covid/papers.csv +++ b/data/covid/papers.csv @@ -5,8 +5,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 35913410,https://doi.org/10.1093/cid/ciac629,Validity of Self-testing at Home With Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Detection by Lateral Flow Immunoassay.,"Atchison CJ, Moshe M, Brown JC, Whitaker M, Wong NCK, Bharath AA, McKendry RA, Darzi A, Ashby D, Donnelly CA, Riley S, Elliott P, Barclay WS, Cooke GS, Ward H.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2023,2023-02-01,Y,Antibodies; Lateral Flow Immunoassay; Home-testing; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ECLIA with virus neutralization.",,doi:https://doi.org/10.1093/cid/ciac629; html:https://europepmc.org/articles/PMC9384551; pdf:https://europepmc.org/articles/PMC9384551?pdf=render 36261315,https://doi.org/10.1002/ana.26536,Fewer COVID-19 Neurological Complications with Dexamethasone and Remdesivir. ,"Grundmann A, Wu CH, Hardwick M, Baillie JK, Openshaw PJM, Semple MG, Böhning D, Pett S, Michael BD, Thomas RH, Galea I, ISARIC4C investigators.",,Annals of neurology,2023,2022-11-09,Y,,,,"The objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID-19). We used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory-confirmed severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode. Out of 89,297 hospital inpatients, 64,088 had severe COVID-19 and 25,209 had non-hypoxic COVID-19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self-care on discharge, and time to recovery. In patients with severe COVID-19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69-0.83), OR = 0.69 (95% CI = 0.51-0.90), and OR = 0.54 (95% CI = 0.47-0.61), respectively. In patients with non-hypoxic COVID-19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62-0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31-1.15). Treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID-19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. ANN NEUROL 2023;93:88-102.",,doi:https://doi.org/10.1002/ana.26536; html:https://europepmc.org/articles/PMC9874556; pdf:https://europepmc.org/articles/PMC9874556?pdf=render 37407076,https://doi.org/10.1136/bmj-2022-073639,Hospital admissions linked to SARS-CoV-2 infection in children and adolescents: cohort study of 3.2 million first ascertained infections in England.,"Wilde H, Tomlinson C, Mateen BA, Selby D, Kanthimathinathan HK, Ramnarayan P, Du Pre P, Johnson M, Pathan N, Gonzalez-Izquierdo A, Lai AG, Gurdasani D, Pagel C, Denaxas S, Vollmer S, Brown K, CVD-COVID-UK/COVID-IMPACT consortium.",,BMJ (Clinical research ed.),2023,2023-07-05,Y,,,,"

Objective

To describe hospital admissions associated with SARS-CoV-2 infection in children and adolescents.

Design

Cohort study of 3.2 million first ascertained SARS-CoV-2 infections using electronic health care record data.

Setting

England, July 2020 to February 2022.

Participants

About 12 million children and adolescents (age <18 years) who were resident in England.

Main outcome measures

Ascertainment of a first SARS-CoV-2 associated hospital admissions: due to SARS-CoV-2, with SARS-CoV-2 as a contributory factor, incidental to SARS-CoV-2 infection, and hospital acquired SARS-CoV-2.

Results

3 226 535 children and adolescents had a recorded first SARS-CoV-2 infection during the observation period, and 29 230 (0.9%) infections involved a SARS-CoV-2 associated hospital admission. The median length of stay was 2 (interquartile range 1-4) days) and 1710 of 29 230 (5.9%) SARS-CoV-2 associated admissions involved paediatric critical care. 70 deaths occurred in which covid-19 or paediatric inflammatory multisystem syndrome was listed as a cause, of which 55 (78.6%) were in participants with a SARS-CoV-2 associated hospital admission. SARS-CoV-2 was the cause or a contributory factor in 21 000 of 29 230 (71.8%) participants who were admitted to hospital and only 380 (1.3%) participants acquired infection as an inpatient and 7855 (26.9%) participants were admitted with incidental SARS-CoV-2 infection. Boys, younger children (<5 years), and those from ethnic minority groups or areas of high deprivation were more likely to be admitted to hospital (all P<0.001). The covid-19 vaccination programme in England has identified certain conditions as representing a higher risk of admission to hospital with SARS-CoV-2: 11 085 (37.9%) of participants admitted to hospital had evidence of such a condition, and a further 4765 (16.3%) of participants admitted to hospital had a medical or developmental health condition not included in the vaccination programme's list.

Conclusions

Most SARS-CoV-2 associated hospital admissions in children and adolescents in England were due to SARS-CoV-2 or SARS-CoV-2 was a contributory factor. These results should inform future public health initiatives and research.",,doi:https://doi.org/10.1136/bmj-2022-073639; html:https://europepmc.org/articles/PMC10318942; pdf:https://europepmc.org/articles/PMC10318942?pdf=render -37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render 37228015,https://doi.org/10.1371/journal.pbio.3002118,Dynamics of SARS-CoV-2 infection hospitalisation and infection fatality ratios over 23 months in England.,"Eales O, Haw D, Wang H, Atchison C, Ashby D, Cooke GS, Barclay W, Ward H, Darzi A, Donnelly CA, Chadeau-Hyam M, Elliott P, Riley S.",,PLoS biology,2023,2023-05-25,Y,,,,"The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England's mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta's emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.",,doi:https://doi.org/10.1371/journal.pbio.3002118; html:https://europepmc.org/articles/PMC10212114; pdf:https://europepmc.org/articles/PMC10212114?pdf=render +37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render 37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render 36180455,https://doi.org/10.1038/s41598-022-20118-6,"Risk of thrombocytopenic, haemorrhagic and thromboembolic disorders following COVID-19 vaccination and positive test: a self-controlled case series analysis in Wales. ","Torabi F, Bedston S, Lowthian E, Akbari A, Owen RK, Bradley DT, Agrawal U, Collins P, Fry R, Griffiths LJ, Beggs J, Davies G, Hollinghurst J, Lyons J, Abbasizanjani H, Cottrell S, Perry M, Roberts R, Azcoaga-Lorenzo A, Fagbamigbe AF, Shi T, Tsang RSM, Robertson C, Hobbs FDR, de Lusignan S, McCowan C, Gravenor M, Simpson CR, Sheikh A, Lyons RA.",,Scientific reports,2022,2022-09-30,Y,,,,"There is a need for better understanding of the risk of thrombocytopenic, haemorrhagic, thromboembolic disorders following first, second and booster vaccination doses and testing positive for SARS-CoV-2. Self-controlled cases series analysis of 2.1 million linked patient records in Wales between 7th December 2020 and 31st December 2021. Outcomes were the first diagnosis of thrombocytopenic, haemorrhagic and thromboembolic events in primary or secondary care datasets, exposure was defined as 0-28 days post-vaccination or a positive reverse transcription polymerase chain reaction test for SARS-CoV-2. 36,136 individuals experienced either a thrombocytopenic, haemorrhagic or thromboembolic event during the study period. Relative to baseline, our observations show greater risk of outcomes in the periods post-first dose of BNT162b2 for haemorrhagic (IRR 1.47, 95%CI: 1.04-2.08) and idiopathic thrombocytopenic purpura (IRR 2.80, 95%CI: 1.21-6.49) events; post-second dose of ChAdOx1 for arterial thrombosis (IRR 1.14, 95%CI: 1.01-1.29); post-booster greater risk of venous thromboembolic (VTE) (IRR-Moderna 3.62, 95%CI: 0.99-13.17) (IRR-BNT162b2 1.39, 95%CI: 1.04-1.87) and arterial thrombosis (IRR-Moderna 3.14, 95%CI: 1.14-8.64) (IRR-BNT162b2 1.34, 95%CI: 1.15-1.58). Similarly, post SARS-CoV-2 infection the risk was increased for haemorrhagic (IRR 1.49, 95%CI: 1.15-1.92), VTE (IRR 5.63, 95%CI: 4.91, 6.4), arterial thrombosis (IRR 2.46, 95%CI: 2.22-2.71). We found that there was a measurable risk of thrombocytopenic, haemorrhagic, thromboembolic events after COVID-19 vaccination and infection.",,doi:https://doi.org/10.1038/s41598-022-20118-6; html:https://europepmc.org/articles/PMC9524320; pdf:https://europepmc.org/articles/PMC9524320?pdf=render 36356998,https://doi.org/10.1136/bmjopen-2022-063271,"Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.","Swann OV, Lone NI, Harrison EM, Tomlinson LA, Walker AJ, Seaborne MJ, Pollock L, Farrell J, Hall PS, Seth S, Williams TC, Preston J, Ainsworth JS, Semple FF, Baillie JK, Katikireddi SV, Akbari A, Lyons R, Simpson CR, Semple MG, Goldacre B, Brophy S, Sheikh A, Docherty AB.",,BMJ open,2022,2022-11-10,Y,epidemiology; Health Economics; Covid-19; Paediatric Infectious Disease &Amp; Immunisation,,,"

Introduction

SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs.

Methods and analysis

We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection.

Ethics and dissemination

This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.",,doi:https://doi.org/10.1136/bmjopen-2022-063271; html:https://europepmc.org/articles/PMC9659708; pdf:https://europepmc.org/articles/PMC9659708?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063271.full.pdf @@ -45,10 +45,10 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 35387486,https://doi.org/10.1161/circulationaha.121.057888,Genetic Landscape of the ACE2 Coronavirus Receptor.,"Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Viñuela A, Gilly A, Elmståhl S, Dedoussis G, Petrie JR, Polašek O, Folkersen L, Chen Y, Yao C, Võsa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium†, IMI-DIRECT Consortium†, Esko T, Enroth S, Johansson Å, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Michaëlsson K, Pawitan Y, Joshi PK, Baillie JK, Mälarstig A, Reiner AP, Wilson JF, Shen X.",,Circulation,2022,2022-04-07,Y,Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.",,doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render 34514500,https://doi.org/10.1093/infdis/jiab459,The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.,"Kovacevic A, Eggo RM, Baguelin M, Domenech de Cellès M, Opatowski L.",,The Journal of infectious diseases,2022,2022-01-01,Y,Mathematical Modeling; Multiplex Testing; Sars-cov-2; Covid-19 Surveillance; Cocirculating Respiratory Viruses,,,"

Background

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

Methods

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

Results

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

Conclusions

This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.",,doi:https://doi.org/10.1093/infdis/jiab459; html:https://europepmc.org/articles/PMC8763960; pdf:https://europepmc.org/articles/PMC8763960?pdf=render 36834176,https://doi.org/10.3390/ijerph20043477,"Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.","Chandan JS, Brown KR, Simms-Williams N, Bashir NZ, Camaradou J, Heining D, Turner GM, Rivera SC, Hotham R, Minhas S, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Marshall T, Calvert MJ, Haroon S, Aiyegbusi OL, TLC Study.",,International journal of environmental research and public health,2023,2023-02-16,Y,Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-Viral Syndromes; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc),,,"

Background

Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.

Methods

We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.

Findings

Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.

Interpretation

In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.

Registration

The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render -37363797,https://doi.org/10.1016/j.lanepe.2023.100653,Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Lancet regional health. Europe,2023,2023-05-16,Y,Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic,,,"

Background

The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.

Methods

With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.

Findings

Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).

Interpretation

An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.

Funding

This work was supported by Health Data Research UK and by National Institute for Health Research.",,doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render 34148733,https://doi.org/10.1016/j.bja.2021.05.018,Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.,"Abbott TEF, Fowler AJ, Dobbs TD, Gibson J, Shahid T, Dias P, Akbari A, Whitaker IS, Pearse RM.",,British journal of anaesthesia,2021,2021-06-11,Y,Surgery; Anaesthesia; epidemiology; Public Policy; Covid-19,,,"

Background

The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery.

Methods

Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI).

Results

We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001).

Conclusions

The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.",,doi:https://doi.org/10.1016/j.bja.2021.05.018; html:https://europepmc.org/articles/PMC8192173; pdf:https://europepmc.org/articles/PMC8192173?pdf=render -35038629,https://doi.org/10.1016/j.puhe.2021.12.010,Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.,"Bradley DT, Murphy S, McWilliams P, Arnold S, Lavery S, Murphy J, de Lusignan S, Hobbs R, Tsang RSM, Akbari A, Torabi F, Beggs J, Chuter A, Shi T, Vasileiou E, Robertson C, Sheikh A, Reid H, O'Reilly D.",,Public health,2022,2021-12-18,Y,Vaccination; outbreak; Care Homes; Covid-19; Sars-cov-2,,,"

Objectives

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

Study design

We undertook an ecological study using routinely available national data.

Methods

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

Results

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

Conclusions

These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.",,doi:https://doi.org/10.1016/j.puhe.2021.12.010; html:https://europepmc.org/articles/PMC8683272; pdf:https://europepmc.org/articles/PMC8683272?pdf=render +37363797,https://doi.org/10.1016/j.lanepe.2023.100653,Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Lancet regional health. Europe,2023,2023-05-16,Y,Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic,,,"

Background

The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.

Methods

With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.

Findings

Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).

Interpretation

An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.

Funding

This work was supported by Health Data Research UK and by National Institute for Health Research.",,doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render 34430796,https://doi.org/10.1016/j.mayocpiqo.2021.08.011,Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.,"Rowlands AV, Dempsey PC, Gillies C, Kloecker DE, Razieh C, Chudasama Y, Islam N, Zaccardi F, Lawson C, Norris T, Davies MJ, Khunti K, Yates T.",,"Mayo Clinic proceedings. Innovations, quality & outcomes",2021,2021-08-20,Y,"Mvpa, Moderate To Vigorous Physical Activity; Covid-19, Coronavirus Disease 2019; Sars-cov-2, Severe Acute Respiratory Syndrome Coronavirus 2",,,"

Objective

To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes.

Methods

Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting). Logistic regressions were used to assess associations with moderate to vigorous physical activity (MVPA), total activity, and intensity gradient. A higher intensity gradient indicates a higher proportion of vigorous activity.

Results

Average MVPA was 48.1 (32.7) min/d. Physical activity was associated with lower odds of severe COVID-19 (adjusted odds ratio per standard deviation increase: MVPA, 0.75 [95% CI, 0.67 to 0.85]; total, 0.83 [0.74 to 0.92]; intensity, 0.77 [0.70 to 0.86]), with stronger associations in women (MVPA, 0.63 [0.52 to 0.77]; total, 0.76 [0.64 to 0.90]; intensity, 0.63 [0.53 to 0.74]) than in men (MVPA, 0.84 [0.73 to 0.97]; total, 0.88 [0.77 to 1.01]; intensity, 0.88 [0.77 to 1.00]). In contrast, when mutually adjusted, total activity was associated with higher odds of a nonsevere infection (1.10 [1.04 to 1.16]), whereas the intensity gradient was associated with lower odds (0.91 [0.86 to 0.97]).

Conclusion

Odds of severe COVID-19 were approximately 25% lower per standard deviation (∼30 min/d) MVPA. A greater proportion of vigorous activity was associated with lower odds of severe and nonsevere infections. The association between total activity and higher odds of a nonsevere infection may be through greater community engagement and thus more exposure to the virus. Results support calls for public health messaging highlighting the potential of MVPA for reducing the odds of severe COVID-19.",,doi:https://doi.org/10.1016/j.mayocpiqo.2021.08.011; html:https://europepmc.org/articles/PMC8376658; pdf:https://europepmc.org/articles/PMC8376658?pdf=render +35038629,https://doi.org/10.1016/j.puhe.2021.12.010,Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.,"Bradley DT, Murphy S, McWilliams P, Arnold S, Lavery S, Murphy J, de Lusignan S, Hobbs R, Tsang RSM, Akbari A, Torabi F, Beggs J, Chuter A, Shi T, Vasileiou E, Robertson C, Sheikh A, Reid H, O'Reilly D.",,Public health,2022,2021-12-18,Y,Vaccination; outbreak; Care Homes; Covid-19; Sars-cov-2,,,"

Objectives

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

Study design

We undertook an ecological study using routinely available national data.

Methods

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

Results

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

Conclusions

These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.",,doi:https://doi.org/10.1016/j.puhe.2021.12.010; html:https://europepmc.org/articles/PMC8683272; pdf:https://europepmc.org/articles/PMC8683272?pdf=render 35858680,https://doi.org/10.1136/bmj-2021-068946,Comparative effectiveness of ChAdOx1 versus BNT162b2 covid-19 vaccines in health and social care workers in England: cohort study using OpenSAFELY.,"Hulme WJ, Williamson EJ, Green ACA, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson LA, Palmer T, Horne EMF, MacKenna B, Morton CE, Mehrkar A, Morley J, Fisher L, Bacon SCJ, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AYS, Mathur R, Wing K, Forbes H, Grint DJ, Douglas IJ, Evans SJW, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JAC, Hernán MA, Goldacre B.",,BMJ (Clinical research ed.),2022,2022-07-20,Y,,,,"

Objective

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

Design

Cohort study, emulating a comparative effectiveness trial, on behalf of NHS England.

Setting

Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 Alpha variant was dominant.

Participants

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

Interventions

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

Main outcome measures

Recorded SARS-CoV-2 positive test, or covid-19 related attendance at an accident and emergency (A&E) department or hospital admission occurring within 20 weeks of receipt of the first vaccine dose.

Results

Over the duration of 118 771 person-years of follow-up there were 6962 positive SARS-CoV-2 tests, 282 covid-19 related A&E attendances, and 166 covid-19 related hospital admissions. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks after vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 20 weeks after first-dose vaccination with BNT162b2 was 21.7 per 1000 people (95% confidence interval 20.9 to 22.4) and with ChAdOx1 was 23.7 (21.8 to 25.6), representing a difference of 2.04 per 1000 people (0.04 to 4.04). The difference in the cumulative incidence per 1000 people of covid-19 related A&E attendance at 20 weeks was 0.06 per 1000 people (95% CI -0.31 to 0.43). For covid-19 related hospital admission, this difference was 0.11 per 1000 people (-0.22 to 0.44).

Conclusions

In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or covid-19 disease up to 20 weeks after vaccination. Incidence dropped sharply at 3-4 weeks after vaccination, and there were few covid-19 related hospital attendance and admission events after this period. This is in line with expected onset of vaccine induced immunity and suggests strong protection against Alpha variant covid-19 disease for both vaccines in this relatively young and healthy population of healthcare workers.",,doi:https://doi.org/10.1136/bmj-2021-068946; html:https://europepmc.org/articles/PMC9295078; pdf:https://europepmc.org/articles/PMC9295078?pdf=render; pdf:https://www.bmj.com/content/bmj/378/bmj-2021-068946.full.pdf 37343968,https://doi.org/10.1136/bmj-2022-072976,Risk prediction of covid-19 related death or hospital admission in adults testing positive for SARS-CoV-2 infection during the omicron wave in England (QCOVID4): cohort study.,"Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CAC.",,BMJ (Clinical research ed.),2023,2023-06-21,Y,,,,"

Objectives

To derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digital.

Design

Cohort study.

Setting

QResearch database linked to English national data on covid-19 vaccinations, SARS-CoV-2 test results, hospital admissions, and cancer and mortality data, 11 December 2021 to 31 March 2022, with follow-up to 30 June 2022.

Participants

1.3 million adults in the derivation cohort and 0.15 million adults in the validation cohort, aged 18-100 years, with a positive test result for SARS-CoV-2 infection.

Main outcome measures

Primary outcome was covid-19 related death and secondary outcome was hospital admission for covid-19. Risk equations with predictor variables were derived from models fitted in the derivation cohort. Performance was evaluated in a separate validation cohort.

Results

Of 1 297 922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18 756 (1.5%) had a covid-19 related hospital admission and 3878 (0.3%) had a covid-19 related death during follow-up. The final QCOVID4 models included age, deprivation score and a range of health and sociodemographic factors, number of covid-19 vaccinations, and previous SARS-CoV-2 infection. The risk of death related to covid-19 was lower among those who had received a covid-19 vaccine, with evidence of a dose-response relation (42% risk reduction associated with one vaccine dose and 92% reduction with four or more doses in men). Previous SARS-CoV-2 infection was associated with a reduction in the risk of covid-19 related death (49% reduction in men). The QCOVID4 algorithm for covid-19 explained 76.0% (95% confidence interval 73.9% to 78.2%) of the variation in time to covid-19 related death in men with a D statistic of 3.65 (3.43 to 3.86) and Harrell's C statistic of 0.970 (0.962 to 0.979). Results were similar for women. QCOVID4 was well calibrated. QCOVID4 was substantially more efficient than the NHS Digital algorithm for correctly identifying patients at high risk of covid-19 related death. Of the 461 covid-19 related deaths in the validation cohort, 333 (72.2%) were in the QCOVID4 high risk group and 95 (20.6%) in the NHS Digital high risk group.

Conclusion

The QCOVID4 risk algorithm, modelled from data during the period when the omicron variant of the SARS-CoV-2 virus was predominant in England, now includes vaccination dose and previous SARS-CoV-2 infection, and predicted covid-19 related death among people with a positive test result. QCOVID4 more accurately identified individuals at the highest levels of absolute risk for targeted interventions than the approach adopted by NHS Digital. QCOVID4 performed well and could be used for targeting treatments for covid-19 disease.",,doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render 35380004,https://doi.org/10.1042/bcj20220105,Development of a colorimetric assay for the detection of SARS-CoV-2 3CLpro activity.,"Garland GD, Harvey RF, Mulroney TE, Monti M, Fuller S, Haigh R, Gerber PP, Barer MR, Matheson NJ, Willis AE.",,The Biochemical journal,2022,2022-04-01,Y,Coronavirus; Assay Development; Covid 19,,,"Diagnostic testing continues to be an integral component of the strategy to contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) global pandemic, the causative agent of Coronavirus Disease 2019 (COVID-19). The SARS-CoV-2 genome encodes the 3C-like protease (3CLpro) which is essential for coronavirus replication. This study adapts an in vitro colorimetric gold nanoparticle (AuNP) based protease assay to specifically detect the activity of SARS-CoV-2 3CLpro as a purified recombinant protein and as a cellular protein exogenously expressed in HEK293T human cells. We also demonstrate that the specific sensitivity of the assay for SARS-CoV-2 3CLpro can be improved by use of an optimised peptide substrate and through hybrid dimerisation with inactive 3CLpro mutant monomers. These findings highlight the potential for further development of the AuNP protease assay to detect SARS-CoV-2 3CLpro activity as a novel, accessible and cost-effective diagnostic test for SARS-CoV-2 infection at the point-of-care. Importantly, this versatile assay could also be easily adapted to detect specific protease activity associated with other viruses or diseases conditions.",,doi:https://doi.org/10.1042/BCJ20220105; html:https://europepmc.org/articles/PMC9162461; pdf:https://europepmc.org/articles/PMC9162461?pdf=render @@ -89,7 +89,7 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 36572492,https://doi.org/10.1136/bmjopen-2022-065862,"Variability and performance of NHS England's 'reason to reside' criteria in predicting hospital discharge in acute hospitals in England: a retrospective, observational cohort study.","Sapey E, Gallier S, Evison F, McNulty D, Reeves K, Ball S.",,BMJ open,2022,2022-12-26,Y,Information management; Health Policy; Quality In Health Care,,,"

Objectives

NHS England (NHSE) advocates 'reason to reside' (R2R) criteria to support discharge planning. The proportion of patients without R2R and their rate of discharge are reported daily by acute hospitals in England. R2R has no interoperable standardised data model (SDM), and its performance has not been validated. We aimed to understand the degree of intercentre and intracentre variation in R2R-related metrics reported to NHSE, define an SDM implemented within a single centre Electronic Health Record to generate an electronic R2R (eR2R) and evaluate its performance in predicting subsequent discharge.

Design

Retrospective observational cohort study using routinely collected health data.

Setting

122 NHS Trusts in England for national reporting and an acute hospital in England for local reporting.

Participants

6 602 706 patient-days were analysed using 3-month national data and 1 039 592 patient-days, using 3-year single centre data.

Main outcome measures

Variability in R2R-related metrics reported to NHSE. Performance of eR2R in predicting discharge within 24 hours.

Results

There were high levels of intracentre and intercentre variability in R2R-related metrics (p<0.0001) but not in eR2R. Informedness of eR2R for discharge within 24 hours was low (J-statistic 0.09-0.12 across three consecutive years). In those remaining in hospital without eR2R, 61.2% met eR2R criteria on subsequent days (76% within 24 hours), most commonly due to increased NEWS2 (21.9%) or intravenous therapy administration (32.8%).

Conclusions

Reported R2R metrics are highly variable between and within acute Trusts in England. Although case-mix or community care provision may account for some variability, the absence of a SDM prevents standardised reporting. Following the development of a SDM in one acute Trust, the variability reduced. However, the performance of eR2R was poor, prone to change even when negative and unable to meaningfully contribute to discharge planning.",,doi:https://doi.org/10.1136/bmjopen-2022-065862; html:https://europepmc.org/articles/PMC9805825; pdf:https://europepmc.org/articles/PMC9805825?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e065862.full.pdf 36302124,https://doi.org/10.1080/21645515.2022.2127572,Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.,"Ohaeri C, Thomas DR, Salmon J, Cottrell S, Lyons J, Akbari A, Lyons RA, Torabi F, Davies GG, Williams C.",,Human vaccines & immunotherapeutics,2022,2022-10-27,Y,Vaccines; Coronavirus; Cerebral Venous Sinus Thrombosis; Cerebral Venous Thrombosis; Covid19,,,"To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.",,doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?pdf=render; doi:https://doi.org/10.1080/21645515.2022.2127572 35813280,https://doi.org/10.1016/s2666-7568(22)00118-0,Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study.,"Tut G, Lancaster T, Sylla P, Butler MS, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Ayodele M, Bone D, Tut E, Bruton R, Krutikov M, Giddings R, Shrotri M, Azmi B, Fuller C, Baynton V, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"

Background

Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs).

Methods

In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified.

Findings

Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39-61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80-92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72-100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds vs 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89-374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30-206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production.

Interpretation

These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination.

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(22)00118-0; html:https://europepmc.org/articles/PMC9252532; pdf:https://europepmc.org/articles/PMC9252532?pdf=render -36691170,https://doi.org/10.1136/bmjopen-2022-061344,"Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK.","Marchant E, Lowthian E, Crick T, Griffiths LJ, Fry R, Dadaczynski K, Okan O, James M, Cowley L, Torabi F, Kennedy J, Akbari A, Lyons R, Brophy S.",,BMJ open,2022,2022-09-07,Y,epidemiology; Public Health; Community Child Health; Covid-19,,,"

Objectives

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

Design

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

Setting

Children attending primary schools in Wales (2018-2020), UK, who were part of the Health and Attainment of Pupils in a Primary Education Network (HAPPEN)_school network.

Participants

Complete linked records of eligible participants were obtained for n=7062 individuals. 39.1% (n=2764) were tested (age 10.6±0.9; 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0; 54.5% girls).

Main outcome measures

Logistic regression of health-related behaviours and demographics were used to determine the ORs of factors associated with (1) being tested for SARS-CoV-2 and (2) testing positive for SARS-CoV-2.

Results

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

Conclusions

Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include coparticipation with others and exposure to SARS-CoV-2. A risk-versus-benefit approach must be considered in relation to promoting these health behaviours, given the importance of health-related behaviours such as childhood physical activity for development.",,doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?pdf=render +36691170,https://doi.org/10.1136/bmjopen-2022-061344,"Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK.","Marchant E, Lowthian E, Crick T, Griffiths LJ, Fry R, Dadaczynski K, Okan O, James M, Cowley L, Torabi F, Kennedy J, Akbari A, Lyons R, Brophy S.",,BMJ open,2022,2022-09-07,Y,epidemiology; Public Health; Community Child Health; Covid-19,,,"

Objectives

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

Design

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

Setting

Children attending primary schools in Wales (2018-2020), UK, who were part of the Health and Attainment of Pupils in a Primary Education Network (HAPPEN)_school network.

Participants

Complete linked records of eligible participants were obtained for n=7062 individuals. 39.1% (n=2764) were tested (age 10.6±0.9; 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0; 54.5% girls).

Main outcome measures

Logistic regression of health-related behaviours and demographics were used to determine the ORs of factors associated with (1) being tested for SARS-CoV-2 and (2) testing positive for SARS-CoV-2.

Results

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

Conclusions

Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include coparticipation with others and exposure to SARS-CoV-2. A risk-versus-benefit approach must be considered in relation to promoting these health behaviours, given the importance of health-related behaviours such as childhood physical activity for development.",,doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e061344.full.pdf 36669966,https://doi.org/10.1016/j.vaccine.2023.01.023,COVID-19 booster vaccination uptake and infection breakthrough amongst health care workers in Wales: A national prospective cohort study.,"Bedston S, Lowthian E, Jarvis CI, Akbari A, Beggs J, Bradley D, de Lusignan S, Griffiths R, Herbert L, Hobbs R, Kerr S, Lyons J, Midgley W, Owen RK, Quint JK, Tsang R, Torabi F, Sheikh A, Lyons RA.",,Vaccine,2023,2023-01-13,Y,Uptake; Vaccination; Health care workers; Booster; Breakthrough; Covid-19,,,"

Background

From September 2021, Health Care Workers (HCWs) in Wales began receiving a COVID-19 booster vaccination. This is the first dose beyond the primary vaccination schedule. Given the emergence of new variants, vaccine waning vaccine, and increasing vaccination hesitancy, there is a need to understand booster vaccine uptake and subsequent breakthrough in this high-risk population.

Methods

We conducted a prospective, national-scale, observational cohort study of HCWs in Wales using anonymised, linked data from the SAIL Databank. We analysed uptake of COVID-19 booster vaccinations from September 2021 to February 2022, with comparisons against uptake of the initial primary vaccination schedule. We also analysed booster breakthrough, in the form of PCR-confirmed SARS-Cov-2 infection, comparing to the second primary dose. Cox proportional hazard models were used to estimate associations for vaccination uptake and breakthrough regarding staff roles, socio-demographics, household composition, and other factors.

Results

We derived a cohort of 73,030 HCWs living in Wales (78% female, 60% 18-49 years old). Uptake was quickest amongst HCWs aged 60 + years old (aHR 2.54, 95%CI 2.45-2.63), compared with those aged 18-29. Asian HCWs had quicker uptake (aHR 1.18, 95%CI 1.14-1.22), whilst Black HCWs had slower uptake (aHR 0.67, 95%CI 0.61-0.74), compared to white HCWs. HCWs residing in the least deprived areas were slightly quicker to have received a booster dose (aHR 1.12, 95%CI 1.09-1.16), compared with those in the most deprived areas. Strongest associations with breakthrough infections were found for those living with children (aHR 1.52, 95%CI 1.41-1.63), compared to two-adult only households. HCWs aged 60 + years old were less likely to get breakthrough infections, compared to those aged 18-29 (aHR 0.42, 95%CI 0.38-0.47).

Conclusion

Vaccination uptake was consistently lower among black HCWs, as well as those from deprived areas. Whilst breakthrough infections were highest in households with children.",,doi:https://doi.org/10.1016/j.vaccine.2023.01.023; html:https://europepmc.org/articles/PMC9837216; pdf:https://europepmc.org/articles/PMC9837216?pdf=render 36224173,https://doi.org/10.1038/s41467-022-33415-5,Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.,"Hastie CE, Lowe DJ, McAuley A, Winter AJ, Mills NL, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2022,2022-10-12,Y,,,,"With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.",,doi:https://doi.org/10.1038/s41467-022-33415-5; html:https://europepmc.org/articles/PMC9556711; pdf:https://europepmc.org/articles/PMC9556711?pdf=render 33893241,https://doi.org/10.1126/science.abf0874,Resurgence of SARS-CoV-2: Detection by community viral surveillance.,"Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,"Science (New York, N.Y.)",2021,2021-04-23,Y,,,,"Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has mainly relied on case reporting, which is biased by health service performance, test availability, and test-seeking behaviors. We report a community-wide national representative surveillance program in England based on self-administered swab results from ~594,000 individuals tested for SARS-CoV-2, regardless of symptoms, between May and the beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared with cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.",,doi:https://doi.org/10.1126/science.abf0874; html:https://europepmc.org/articles/PMC8158959; pdf:https://europepmc.org/articles/PMC8158959?pdf=render; pdf:https://www.science.org/cms/asset/00326f17-60ca-4c01-8814-727df6504005/pap.pdf @@ -163,14 +163,14 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34942103,https://doi.org/10.1016/s0140-6736(21)02754-9,"Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.","Katikireddi SV, Cerqueira-Silva T, Vasileiou E, Robertson C, Amele S, Pan J, Taylor B, Boaventura V, Werneck GL, Flores-Ortiz R, Agrawal U, Docherty AB, McCowan C, McMenamin J, Moore E, Ritchie LD, Rudan I, Shah SA, Shi T, Simpson CR, Barreto ML, Oliveira VA, Barral-Netto M, Sheikh A.",,"Lancet (London, England)",2022,2021-12-20,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render 33243817,https://doi.org/10.1136/bmjopen-2020-042813,COVID-19 in Pregnancy in Scotland (COPS): protocol for an observational study using linked Scottish national data.,"Stock SJ, McAllister D, Vasileiou E, Simpson CR, Stagg HR, Agrawal U, McCowan C, Hopkins L, Donaghy J, Ritchie L, Robertson C, Sheikh A, Wood R.",,BMJ open,2020,2020-11-26,Y,Obstetrics; epidemiology; Neonatology; Perinatology; Covid-19,,,"

Introduction

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

Methods and analysis

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

Ethics and dissemination

COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2020-042813; html:https://europepmc.org/articles/PMC7691999; pdf:https://europepmc.org/articles/PMC7691999?pdf=render -36451358,https://doi.org/10.1016/j.nicl.2022.103253,Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study.,"Tsvetanov KA, Spindler LRB, Stamatakis EA, Newcombe VFJ, Lupson VC, Chatfield DA, Manktelow AE, Outtrim JG, Elmer A, Kingston N, Bradley JR, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, NIHR COVID-19 BioResource, Cambridge NIHR Clinical Research Facility, CITIID-NIHR BioResource COVID-19 Collaboration.",,NeuroImage. Clinical,2022,2022-11-07,Y,Cerebrovascular; Microvascular; Neurology; Cardiorespiratory; Covid-19; Sars-cov-2,,,"Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. We studied the chronic effect of COVID-19 on cerebrovascular health, in relation to acute severity, adverse clinical outcomes and in contrast to control group data. Here we assess cerebrovascular health in 45 patients six months after hospitalisation for acute COVID-19 using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Acute COVID-19 severity was indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. Chronic widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. The level of cerebrovascular dysfunction was associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.",,doi:https://doi.org/10.1016/j.nicl.2022.103253; html:https://europepmc.org/articles/PMC9639388; pdf:https://europepmc.org/articles/PMC9639388?pdf=render 32873607,https://doi.org/10.1136/bmjresp-2020-000644,Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area.,"Sapey E, Gallier S, Mainey C, Nightingale P, McNulty D, Crothers H, Evison F, Reeves K, Pagano D, Denniston AK, Nirantharakumar K, Diggle P, Ball S, All clinicians and students at University Hospitals Birmingham NHS Foundation Trust.",,BMJ open respiratory research,2020,2020-09-01,Y,Viral infection; respiratory infection; Clinical Epidemiology,,,"

Background

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

Methods

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

Results

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

Conclusions

Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.",,doi:https://doi.org/10.1136/bmjresp-2020-000644; html:https://europepmc.org/articles/PMC7467523; pdf:https://europepmc.org/articles/PMC7467523?pdf=render +36451358,https://doi.org/10.1016/j.nicl.2022.103253,Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study.,"Tsvetanov KA, Spindler LRB, Stamatakis EA, Newcombe VFJ, Lupson VC, Chatfield DA, Manktelow AE, Outtrim JG, Elmer A, Kingston N, Bradley JR, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, NIHR COVID-19 BioResource, Cambridge NIHR Clinical Research Facility, CITIID-NIHR BioResource COVID-19 Collaboration.",,NeuroImage. Clinical,2022,2022-11-07,Y,Cerebrovascular; Microvascular; Neurology; Cardiorespiratory; Covid-19; Sars-cov-2,,,"Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. We studied the chronic effect of COVID-19 on cerebrovascular health, in relation to acute severity, adverse clinical outcomes and in contrast to control group data. Here we assess cerebrovascular health in 45 patients six months after hospitalisation for acute COVID-19 using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Acute COVID-19 severity was indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. Chronic widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. The level of cerebrovascular dysfunction was associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.",,doi:https://doi.org/10.1016/j.nicl.2022.103253; html:https://europepmc.org/articles/PMC9639388; pdf:https://europepmc.org/articles/PMC9639388?pdf=render 33728401,https://doi.org/10.1038/s42254-020-0178-4,Modelling COVID-19.,"Vespignani A, Tian H, Dye C, Lloyd-Smith JO, Eggo RM, Shrestha M, Scarpino SV, Gutierrez B, Kraemer MUG, Wu J, Leung K, Leung GM.",,Nature reviews. Physics,2020,2020-05-06,Y,Applied Mathematics; Complex Networks,,,"As the COVID-19 pandemic continues, mathematical epidemiologists share their views on what models reveal about how the disease has spread, the current state of play and what work still needs to be done.",Vespignani et al. used mathematical models to model the epidemic of covid-19 and to predict future scenarios for possible interventions and inform policy and practice.,doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render 35595824,https://doi.org/10.1038/s41598-022-12517-6,Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK.,"Waites W, Pearson CAB, Gaskell KM, House T, Pellis L, Johnson M, Gould V, Hunt A, Stone NRH, Kasstan B, Chantler T, Lal S, Roberts CH, Goldblatt D, CMMID COVID-19 Working Group, Marks M, Eggo RM.",,Scientific reports,2022,2022-05-20,Y,,,,"Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.",,doi:https://doi.org/10.1038/s41598-022-12517-6; html:https://europepmc.org/articles/PMC9121858; pdf:https://europepmc.org/articles/PMC9121858?pdf=render -36691218,https://doi.org/10.1136/bmjopen-2021-059813,Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study.,"Evans BA, Akbari A, Bailey R, Bethell L, Bufton S, Carson-Stevens A, Dixon L, Edwards A, John A, Jolles S, Kingston MR, Lyons J, Lyons R, Porter A, Sewell B, Thornton CA, Watkins A, Whiffen T, Snooks H.",,BMJ open,2022,2022-09-08,Y,immunology; Public Health; Health Policy; Covid-19,,,"

Introduction

Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics.

Methods and analysis

This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results; use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes; survey a stratified random sample of each group about activities and quality of life at 12 months; use routine and newly collected blood data to assess immunity; interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences; collect healthcare resource use data to calculate implementation costs and cost-consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study.

Ethics and dissemination

The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks.",,doi:https://doi.org/10.1136/bmjopen-2021-059813; html:https://europepmc.org/articles/PMC9461087; pdf:https://europepmc.org/articles/PMC9461087?pdf=render 34174193,https://doi.org/10.1016/s1473-3099(21)00289-9,Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.,"Shrotri M, Krutikov M, Palmer T, Giddings R, Azmi B, Subbarao S, Fuller C, Irwin-Singer A, Davies D, Tut G, Lopez Bernal J, Moss P, Hayward A, Copas A, Shallcross L.",,The Lancet. Infectious diseases,2021,2021-06-23,Y,,,,"

Background

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination.

Methods

The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421.

Findings

10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001).

Interpretation

Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities.

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738; doi:https://doi.org/10.1016/s1473-3099(21)00289-9 -35143473,https://doi.org/10.1371/journal.pbio.3001531,SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.,"Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.",,PLoS biology,2022,2022-02-10,Y,,,,"Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.",,doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render +36691218,https://doi.org/10.1136/bmjopen-2021-059813,Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study.,"Evans BA, Akbari A, Bailey R, Bethell L, Bufton S, Carson-Stevens A, Dixon L, Edwards A, John A, Jolles S, Kingston MR, Lyons J, Lyons R, Porter A, Sewell B, Thornton CA, Watkins A, Whiffen T, Snooks H.",,BMJ open,2022,2022-09-08,Y,immunology; Public Health; Health Policy; Covid-19,,,"

Introduction

Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics.

Methods and analysis

This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results; use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes; survey a stratified random sample of each group about activities and quality of life at 12 months; use routine and newly collected blood data to assess immunity; interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences; collect healthcare resource use data to calculate implementation costs and cost-consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study.

Ethics and dissemination

The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks.",,doi:https://doi.org/10.1136/bmjopen-2021-059813; html:https://europepmc.org/articles/PMC9461087; pdf:https://europepmc.org/articles/PMC9461087?pdf=render 33222494,https://doi.org/10.1177/2048872620974605,Cardiac complications in patients hospitalised with COVID-19.,"Linschoten M, Peters S, van Smeden M, Jewbali LS, Schaap J, Siebelink HM, Smits PC, Tieleman RG, van der Harst P, van Gilst WH, Asselbergs FW, CAPACITY-COVID collaborative consortium.",,European heart journal. Acute cardiovascular care,2020,2020-11-21,Y,Pulmonary embolism; Cohorts; Cardiac Complications; Patient Registry; Covid-19/coronavirus,,,"

Aims

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

Methods and results

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

Conclusion

This large study among 3011 hospitalised patients with COVID-19 shows that the incidence of cardiac complications during hospital admission is low, despite a frequent history of cardiovascular disease. Long-term cardiac outcomes and the role of pre-existing cardiovascular disease in COVID-19 outcome warrants further investigation.",,doi:https://doi.org/10.1177/2048872620974605; html:https://europepmc.org/articles/PMC7734244; pdf:https://europepmc.org/articles/PMC7734244?pdf=render +35143473,https://doi.org/10.1371/journal.pbio.3001531,SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.,"Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.",,PLoS biology,2022,2022-02-10,Y,,,,"Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.",,doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render 36721385,https://doi.org/10.1002/pul2.12192,Reduced circulating BMP9 and pBMP10 in hospitalized COVID-19 patients.,"Dunmore BJ, Upton PD, Auckland K, Samanta RJ, CITIID‐NIHR BioResource COVID‐19 Collaboration, EpiCov Database, Lyons PA, Smith KGC, Gräf S, Summers C, Morrell NW.",,Pulmonary circulation,2023,2023-01-01,Y,Endothelial Cell Dysfunction; Bmps; Viral Infections And Pathogenesis,,,"Similar to other causes of acute respiratory distress syndrome, coronavirus disease 2019 (COVID-19) is characterized by the aberrant expression of vascular injury biomarkers. We present the first report that circulating plasma bone morphogenetic proteins (BMPs), BMP9 and pBMP10, involved in vascular protection, are reduced in hospitalized patients with COVID-19.",,doi:https://doi.org/10.1002/pul2.12192; html:https://europepmc.org/articles/PMC9881210; pdf:https://europepmc.org/articles/PMC9881210?pdf=render 36647111,https://doi.org/10.1186/s12911-022-02093-0,"Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration.","Abbasizanjani H, Torabi F, Bedston S, Bolton T, Davies G, Denaxas S, Griffiths R, Herbert L, Hollings S, Keene S, Khunti K, Lowthian E, Lyons J, Mizani MA, Nolan J, Sudlow C, Walker V, Whiteley W, Wood A, Akbari A, CVD-COVID-UK/COVID-IMPACT Consortium.",,BMC medical informatics and decision making,2023,2023-01-16,Y,Population Health; Electronic Health Record; Reproducible Research; Common Data Model; Data Harmonisation; Sail Databank; Covid-19; Trusted Research Environments; Nhs Digital Tre For England,,,"

Background

The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt.

Methods

Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer.

Results

Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information.

Conclusions

We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.",,doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?pdf=render 35531432,https://doi.org/10.1016/s2666-7568(22)00093-9,"Outcomes of SARS-CoV-2 omicron infection in residents of long-term care facilities in England (VIVALDI): a prospective, cohort study.","Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, COVID-19 Genomics UK consortium.",,The lancet. Healthy longevity,2022,2022-05-04,Y,,,,"

Background

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

Methods

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

Results

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

Interpretation

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

Funding

UK Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(22)00093-9; html:https://europepmc.org/articles/PMC9067940; pdf:https://europepmc.org/articles/PMC9067940?pdf=render @@ -214,8 +214,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34599903,https://doi.org/10.1016/s2213-2600(21)00380-5,COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II): a prospective cohort study.,"Agrawal U, Katikireddi SV, McCowan C, Mulholland RH, Azcoaga-Lorenzo A, Amele S, Fagbamigbe AF, Vasileiou E, Grange Z, Shi T, Kerr S, Moore E, Murray JLK, Shah SA, Ritchie L, O'Reilly D, Stock SJ, Beggs J, Chuter A, Torabi F, Akbari A, Bedston S, McMenamin J, Wood R, Tang RSM, de Lusignan S, Hobbs FDR, Woolhouse M, Simpson CR, Robertson C, Sheikh A.",,The Lancet. Respiratory medicine,2021,2021-09-29,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Scottish Government, and Health Data Research UK.",,doi:https://doi.org/10.1016/S2213-2600(21)00380-5; html:https://europepmc.org/articles/PMC8480963 34873584,https://doi.org/10.1016/j.eclinm.2021.101212,Disentangling post-vaccination symptoms from early COVID-19.,"Canas LS, Österdahl MF, Deng J, Hu C, Selvachandran S, Polidori L, May A, Molteni E, Murray B, Chen L, Kerfoot E, Klaser K, Antonelli M, Hammers A, Spector T, Ourselin S, Steves C, Sudre CH, Modat M, Duncan EL.",,EClinicalMedicine,2021,2021-12-01,Y,"Vaccination; Side-effects; Early Detection; Mobile Technology; Self-reported Symptoms; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Roc, Receiver Operating Curve; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction; Nhs Uk, National Health Service Of The United Kingdom; Severe Acute Respiratory Syndrome‐Related Coronavirus 2 (Sars-Cov-2); Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Lfat, Lateral Flow Antigen Test; O-az, Oxford-astrazeneca Adenovirus-vectored Vaccine; Pb, Pfizer-bointech Mrna Vaccine; Sars-cov-2, Severe Acute Respiratory Syndrome-related Coronavirus-2; Uk, United Kingdom Of Great Britain And Nothern Ireland; Bmem, Bayesian Mixed-effect Model",,,"

Background

Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.

Methods

We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.

Findings

Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).

Interpretation

Post-vaccination symptoms per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.

Funding

UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.",,doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render 36936592,https://doi.org/10.1136/bmjmed-2022-000151,Covid-19 variants of concern and pregnancy.,"Stock SJ, Harmer C, Calvert C.",,BMJ medicine,2022,2022-03-02,Y,Pregnancy complications; Covid-19,,,,,doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render -36385522,https://doi.org/10.1093/ehjqcco/qcac077,Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.,"Wright FL, Cheema K, Goldacre R, Hall N, Herz N, Islam N, Karim Z, Moreno-Martos D, Morales DR, O'Connell D, Spata E, Akbari A, Ashworth M, Barber M, Briffa N, Canoy D, Denaxas S, Khunti K, Kurdi A, Mamas M, Priedon R, Sudlow C, Morris EJA, Lacey B, Banerjee A.",,European heart journal. Quality of care & clinical outcomes,2023,2023-06-01,Y,,,,"

Background

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

Methods and results

Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions.

Conclusion

The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.",,doi:https://doi.org/10.1093/ehjqcco/qcac077; html:https://europepmc.org/articles/PMC10284263; pdf:https://europepmc.org/articles/PMC10284263?pdf=render; pdf:https://cronfa.swan.ac.uk/Record/cronfa62054/Download/62054__26063__5453b00901174a7d9a0797547f023fba.pdf 34345715,https://doi.org/10.23889/ijpds.v5i4.1656,Establishing the impact of COVID-19 on the health outcomes of domiciliary care workers in Wales using routine data: a protocol for the OSCAR study.,"Lugg-Widger F, Cannings-John R, Akbari A, Brookes-Howell L, Hood K, John A, Jones H, Prout H, Schoenbuchner S, Thomas D, Robling M.",,International journal of population data science,2020,2020-01-01,Y,Mortality; Administrative Data; Natural Experiment; Domiciliary Care Worker; Covid-19,,,"

Introduction

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

Objectives

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

Methods

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

Discussion

Using anonymised linked occupational and EHR data and qualitative interviews, the OSCAR study will quantify the risk of COVID-19 on DCWs' health and explore sources of variation. This will provide a secure base for informing public health policy and occupational guidance.",,doi:https://doi.org/10.23889/ijpds.v5i4.1656; html:https://europepmc.org/articles/PMC8280712; pdf:https://europepmc.org/articles/PMC8280712?pdf=render +36385522,https://doi.org/10.1093/ehjqcco/qcac077,Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.,"Wright FL, Cheema K, Goldacre R, Hall N, Herz N, Islam N, Karim Z, Moreno-Martos D, Morales DR, O'Connell D, Spata E, Akbari A, Ashworth M, Barber M, Briffa N, Canoy D, Denaxas S, Khunti K, Kurdi A, Mamas M, Priedon R, Sudlow C, Morris EJA, Lacey B, Banerjee A.",,European heart journal. Quality of care & clinical outcomes,2023,2023-06-01,Y,,,,"

Background

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

Methods and results

Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions.

Conclusion

The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.",,doi:https://doi.org/10.1093/ehjqcco/qcac077; html:https://europepmc.org/articles/PMC10284263; pdf:https://europepmc.org/articles/PMC10284263?pdf=render; pdf:https://cronfa.swan.ac.uk/Record/cronfa62054/Download/62054__26063__5453b00901174a7d9a0797547f023fba.pdf 35440469,https://doi.org/10.3399/bjgp.2022.0083,"Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.","Dorward J, Yu LM, Hayward G, Saville BR, Gbinigie O, Van Hecke O, Ogburn E, Evans PH, Thomas NP, Patel MG, Richards D, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Shanyinde M, de Lusignan S, Andersson MI, Butler CC, Hobbs FR, PRINCIPLE Trial Collaborative Group.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Colchicine; Community; Primary Health Care; Randomised Controlled Trial; Covid-19,,,"

Background

Colchicine has been proposed as a COVID-19 treatment.

Aim

To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.

Design and setting

Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).

Method

Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models.

Results

The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4).

Conclusion

Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render 35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render 36083213,https://doi.org/10.1093/jamia/ocac158,Translating and evaluating historic phenotyping algorithms using SNOMED CT.,"Elkheder M, Gonzalez-Izquierdo A, Qummer Ul Arfeen M, Kuan V, Lumbers RT, Denaxas S, Shah AD.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-01-01,Y,Terminology; Phenotype; Ontology; Electronic Health Records; Snomed Ct,,,"

Objective

Patient phenotype definitions based on terminologies are required for the computational use of electronic health records. Within UK primary care research databases, such definitions have typically been represented as flat lists of Read terms, but Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) (a widely employed international reference terminology) enables the use of relationships between concepts, which could facilitate the phenotyping process. We implemented SNOMED CT-based phenotyping approaches and investigated their performance in the CPRD Aurum primary care database.

Materials and methods

We developed SNOMED CT phenotype definitions for 3 exemplar diseases: diabetes mellitus, asthma, and heart failure, using 3 methods: ""primary"" (primary concept and its descendants), ""extended"" (primary concept, descendants, and additional relations), and ""value set"" (based on text searches of term descriptions). We also derived SNOMED CT codelists in a semiautomated manner for 276 disease phenotypes used in a study of health across the lifecourse. Cohorts selected using each codelist were compared to ""gold standard"" manually curated Read codelists in a sample of 500 000 patients from CPRD Aurum.

Results

SNOMED CT codelists selected a similar set of patients to Read, with F1 scores exceeding 0.93, and age and sex distributions were similar. The ""value set"" and ""extended"" codelists had slightly greater recall but lower precision than ""primary"" codelists. We were able to represent 257 of the 276 phenotypes by a single concept hierarchy, and for 135 phenotypes, the F1 score was greater than 0.9.

Conclusions

SNOMED CT provides an efficient way to define disease phenotypes, resulting in similar patient populations to manually curated codelists.",,doi:https://doi.org/10.1093/jamia/ocac158; html:https://europepmc.org/articles/PMC9846670; pdf:https://europepmc.org/articles/PMC9846670?pdf=render @@ -243,8 +243,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 32564639,https://doi.org/10.1177/0300060520931298,Mortality statistics in England and Wales: the SARS-CoV-2 paradox.,"Harrison G, Newport D, Robbins T, Arvanitis TN, Stein A.",,The Journal of international medical research,2020,2020-06-01,Y,Respiratory disease; United Kingdom; Mortality Rate; Paradox; Covid-19; Sars-cov-2,,,"

Objective

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

Methods

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

Results

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

Conclusions

Paradoxically, but potentially importantly, lower rather than higher weekly mortality rates were observed during the early stages of the SARS-CoV-2 pandemic. This paradox may have implications for current and future healthcare utilisation. A rebound increase in non-SARS-CoV-2 mortality later this year might coincide with the peak of SARS-CoV-2 admissions and mortality.",,doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render 32485082,https://doi.org/10.1002/ejhf.1924,Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust.,"Bean DM, Kraljevic Z, Searle T, Bendayan R, Kevin O, Pickles A, Folarin A, Roguski L, Noor K, Shek A, Zakeri R, Shah AM, Teo JTH, Dobson RJB.",,European journal of heart failure,2020,2020-06-01,Y,Hypertension; Angiotensin-converting enzyme inhibitors; Disease Outcome; Covid-19,,,"

Aims

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

Methods and results

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

Conclusions

There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.","This study aimed to determine whether or not two specific types of medication (ACE inhibitors and angiotensin-2 blockers - ACEi/ARB) used for hypertension or diabetes are associated with increased risk of severe COVID-19 infection in a sample of 1,200 inpatients (one third of whom were taking the medications under investigation) in two London hospitals. The researchers used data from electonic medical notes and electronic health records. The patients who were taking the medication were, on average, older and had more underlying health conditions than patients who were not. After accounting for these differences in patient health the researchers found that the risk of severe COVID infection was not higher for patients taking ACEi/ARB. This finding is important for patients because it suggests that they should continue to take ACEi/ARB that have been presecribed to them.",doi:https://doi.org/10.1002/ejhf.1924; html:https://europepmc.org/articles/PMC7301045; pdf:https://europepmc.org/articles/PMC7301045?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1924 34011491,https://doi.org/10.1136/bmj.n1137,Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries.,"Islam N, Shkolnikov VM, Acosta RJ, Klimkin I, Kawachi I, Irizarry RA, Alicandro G, Khunti K, Yates T, Jdanov DA, White M, Lewington S, Lacey B.",,BMJ (Clinical research ed.),2021,2021-05-19,Y,,,,"

Objective

To estimate the direct and indirect effects of the covid-19 pandemic on mortality in 2020 in 29 high income countries with reliable and complete age and sex disaggregated mortality data.

Design

Time series study of high income countries.

Setting

Austria, Belgium, Czech Republic, Denmark, England and Wales, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, the Netherlands, New Zealand, Northern Ireland, Norway, Poland, Portugal, Scotland, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, and United States.

Participants

Mortality data from the Short-term Mortality Fluctuations data series of the Human Mortality Database for 2016-20, harmonised and disaggregated by age and sex.

Interventions

Covid-19 pandemic and associated policy measures.

Main outcome measures

Weekly excess deaths (observed deaths versus expected deaths predicted by model) in 2020, by sex and age (0-14, 15-64, 65-74, 75-84, and ≥85 years), estimated using an over-dispersed Poisson regression model that accounts for temporal trends and seasonal variability in mortality.

Results

An estimated 979 000 (95% confidence interval 954 000 to 1 001 000) excess deaths occurred in 2020 in the 29 high income countries analysed. All countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The five countries with the highest absolute number of excess deaths were the US (458 000, 454 000 to 461 000), Italy (89 100, 87 500 to 90 700), England and Wales (85 400, 83 900 to 86 800), Spain (84 100, 82 800 to 85 300), and Poland (60 100, 58 800 to 61 300). New Zealand had lower overall mortality than expected (-2500, -2900 to -2100). In many countries, the estimated number of excess deaths substantially exceeded the number of reported deaths from covid-19. The highest excess death rates (per 100 000) in men were in Lithuania (285, 259 to 311), Poland (191, 184 to 197), Spain (179, 174 to 184), Hungary (174, 161 to 188), and Italy (168, 163 to 173); the highest rates in women were in Lithuania (210, 185 to 234), Spain (180, 175 to 185), Hungary (169, 156 to 182), Slovenia (158, 132 to 184), and Belgium (151, 141 to 162). Little evidence was found of subsequent compensatory reductions following excess mortality.

Conclusion

Approximately one million excess deaths occurred in 2020 in these 29 high income countries. Age standardised excess death rates were higher in men than women in almost all countries. Excess deaths substantially exceeded reported deaths from covid-19 in many countries, indicating that determining the full impact of the pandemic on mortality requires assessment of excess deaths. Many countries had lower deaths than expected in children <15 years. Sex inequality in mortality widened further in most countries in 2020.",,doi:https://doi.org/10.1136/bmj.n1137; html:https://europepmc.org/articles/PMC8132017; pdf:https://europepmc.org/articles/PMC8132017?pdf=render -35226680,https://doi.org/10.1371/journal.pone.0264023,"COVID-19 mitigation measures in primary schools and association with infection and school staff wellbeing: An observational survey linked with routine data in Wales, UK.","Marchant E, Griffiths L, Crick T, Fry R, Hollinghurst J, James M, Cowley L, Abbasizanjani H, Torabi F, Thompson DA, Kennedy J, Akbari A, Gravenor MB, Lyons RA, Brophy S.",,PloS one,2022,2022-02-28,Y,,,,"

Introduction

School-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, two metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation measures and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK.

Methods

A school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank.

Results

Responses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement two metre social distancing from pupils. We did not find evidence that maintaining a two metre distance was associated with lower rates of COVID-19 in the school.

Conclusions

Implementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, two metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.",,doi:https://doi.org/10.1371/journal.pone.0264023; html:https://europepmc.org/articles/PMC8884508; pdf:https://europepmc.org/articles/PMC8884508?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264023&type=printable 32393804,https://doi.org/10.1038/s41591-020-0916-2,Real-time tracking of self-reported symptoms to predict potential COVID-19.,"Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD.",,Nature medicine,2020,2020-05-11,N,,,,"A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.",,doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2; pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf +35226680,https://doi.org/10.1371/journal.pone.0264023,"COVID-19 mitigation measures in primary schools and association with infection and school staff wellbeing: An observational survey linked with routine data in Wales, UK.","Marchant E, Griffiths L, Crick T, Fry R, Hollinghurst J, James M, Cowley L, Abbasizanjani H, Torabi F, Thompson DA, Kennedy J, Akbari A, Gravenor MB, Lyons RA, Brophy S.",,PloS one,2022,2022-02-28,Y,,,,"

Introduction

School-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, two metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation measures and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK.

Methods

A school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank.

Results

Responses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement two metre social distancing from pupils. We did not find evidence that maintaining a two metre distance was associated with lower rates of COVID-19 in the school.

Conclusions

Implementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, two metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.",,doi:https://doi.org/10.1371/journal.pone.0264023; html:https://europepmc.org/articles/PMC8884508; pdf:https://europepmc.org/articles/PMC8884508?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264023&type=printable 34183342,https://doi.org/10.1136/bmjopen-2020-046392,"United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol.","Teece L, Gray LJ, Melbourne C, Orton C, Ford DV, Martin CA, McAllister D, Khunti K, Tobin M, John C, Abrams KR, Pareek M, UK-REACH Study Collaborative Group.",,BMJ open,2021,2021-06-28,Y,epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19,,,"

Introduction

COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.

Methods and analysis

This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.

Ethics and dissemination

Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).

Trial registration number

ISRCTN11811602.",,doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render 32614817,https://doi.org/10.1371/journal.pcbi.1008031,Estimation of country-level basic reproductive ratios for novel Coronavirus (SARS-CoV-2/COVID-19) using synthetic contact matrices.,"Hilton J, Keeling MJ.",,PLoS computational biology,2020,2020-07-02,Y,,,,"The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.",,doi:https://doi.org/10.1371/journal.pcbi.1008031; html:https://europepmc.org/articles/PMC7363110; pdf:https://europepmc.org/articles/PMC7363110?pdf=render 34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render @@ -256,7 +256,6 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34598993,https://doi.org/10.1136/bmjopen-2021-054410,"Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.","Greenbury SF, Longford N, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,BMJ open,2021,2021-10-01,Y,Public Health; Neonatology; Neonatal Intensive & Critical Care,,,"

Objectives

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

Design

Observational cohort study using the UK National Neonatal Research Database.

Setting

England and Wales.

Participants

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

Main outcome measures

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

Methods

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

Results

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

Conclusions

Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.",,doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render 33220850,https://doi.org/10.1016/s0140-6736(20)32465-x,Urgent actions and policies needed to address COVID-19 among UK ethnic minorities.,"Mathur R, Bear L, Khunti K, Eggo RM.",,"Lancet (London, England)",2020,2020-11-19,Y,,,,,,doi:https://doi.org/10.1016/S0140-6736(20)32465-X; html:https://europepmc.org/articles/PMC7831890; pdf:https://europepmc.org/articles/PMC7831890?pdf=render 35369709,https://doi.org/10.1128/jcm.02408-21,SARS-CoV-2 Testing in the Community: Testing Positive Samples with the TaqMan SARS-CoV-2 Mutation Panel To Find Variants in Real Time.,"Ashford F, Best A, Dunn SJ, Ahmed Z, Siddiqui H, Melville J, Wilkinson S, Mirza J, Cumley N, Stockton J, Ferguson J, Wheatley L, Ratcliffe E, Casey A, Plant T, COVID-19 Genomics UK (COG-UK) Consortium, Quick J, Richter A, Loman N, McNally A.",,Journal of clinical microbiology,2022,2022-04-04,Y,PCR; Genotyping; Genome sequencing; SNPs; real time; Sars-cov-2; Variants Of Concern,,,"Genome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages; however, there can be limitations due to sequence dropout when used to identify specific key mutations. Recently, ThermoFisher Scientific has developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the ThermoFisher TaqMan mutation panel genotyping assay, initially for three mutations of concern and then for an additional two mutations of concern, against SARS-CoV-2-positive clinical samples and the corresponding COVID-19 Genomics UK Consortium (COG-UK) sequencing data. We demonstrate that genotyping is a powerful in-depth technique for identifying specific mutations, is an excellent complement to genome sequencing, and has real clinical health value potential, allowing laboratories to report and take action on variants of concern much more quickly.",,doi:https://doi.org/10.1128/jcm.02408-21; html:https://europepmc.org/articles/PMC9020355; pdf:https://europepmc.org/articles/PMC9020355?pdf=render; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020355 -37434746,https://doi.org/10.1016/j.eclinm.2023.102077,"Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.","Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.",,EClinicalMedicine,2023,2023-06-29,Y,Pandemic; Healthcare Utilisation; Ethnic Differences,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).",,doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render 34145260,https://doi.org/10.1038/s41467-021-23935-x,Community factors and excess mortality in first wave of the COVID-19 pandemic in England.,"Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",,Nature communications,2021,2021-06-18,Y,,,,"Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.",,doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render; pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf 37088955,https://doi.org/10.1177/02692163231167212,"Deaths at home, area-based deprivation and the effect of the Covid-19 pandemic: An analysis of mortality data across four nations.","Leniz J, Davies JM, Bone AE, Hocaoglu M, Verne J, Barclay S, Murtagh FEM, Fraser LK, Higginson IJ, Sleeman KE.",,Palliative medicine,2023,2023-04-23,Y,Mortality; Palliative care; Terminal Care; Inequalities; Place Of Death; Deprivation; Pandemics; Socio-economic Position; Covid-19,,,"

Background

The number and proportion of home deaths in the UK increased during the Covid-19 pandemic. It is not known whether these changes were experienced disproportionately by people from different socioeconomic groups.

Aim

To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.

Design

Retrospective cohort study using population-based individual-level mortality data.

Setting/participants

All registered deaths in England, Wales, Scotland and Northern Ireland. The proportion of home deaths between 28th March and 31st December 2020 was compared with the same period in 2019. We used Poisson regression models to evaluate the association between decedent's area-based level of deprivation and risk of home death, as well as the interaction between deprivation and year of death, for each nation separately.

Results

Between the 28th March and 31st December 2020, 409,718 deaths were recorded in England, 46,372 in Scotland, 26,410 in Wales and 13,404 in Northern Ireland. All four nations showed an increase in the adjusted proportion of home deaths between 2019 and 2020, ranging from 21 to 28%. This increase was lowest for people living in the most deprived areas in all nations, with evidence of a deprivation gradient in England.

Conclusions

The Covid-19 pandemic exacerbated a previously described socioeconomic inequality in place of death in the UK. Further research to understand the reasons for this change and if this inequality has been sustained is needed.",,doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882 34782484,https://doi.org/10.1136/thoraxjnl-2021-217580,External validation of the QCovid risk prediction algorithm for risk of COVID-19 hospitalisation and mortality in adults: national validation cohort study in Scotland.,"Simpson CR, Robertson C, Kerr S, Shi T, Vasileiou E, Moore E, McCowan C, Agrawal U, Docherty A, Mulholland R, Murray J, Ritchie LD, McMenamin J, Hippisley-Cox J, Sheikh A.",,Thorax,2022,2021-11-15,Y,Clinical Epidemiology; Covid-19,,,"

Background

The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland.

Methods

We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020.

Results

Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell's C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell's C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively.

Conclusions

Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively.",,doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?pdf=render @@ -270,27 +269,28 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33933530,https://doi.org/10.1016/j.jinf.2021.04.027,Early observations on the impact of a healthcare worker COVID-19 vaccination programme at a major UK tertiary centre.,"Garvey MI, Wilkinson MAC, Holden E, Shields A, Robertson A, Richter A, Ball S.",,The Journal of infection,2021,2021-04-29,Y,Vaccination; Healthcare Workers; Lateral Flow; Covid-19,,,,,doi:https://doi.org/10.1016/j.jinf.2021.04.027; html:https://europepmc.org/articles/PMC8081749; pdf:https://europepmc.org/articles/PMC8081749?pdf=render 34672950,https://doi.org/10.1016/s2213-2600(21)00435-5,"Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The Lancet. Respiratory medicine,2021,2021-10-18,Y,,,,"

Background

Colchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.

Methods

In this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m2, and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/S2213-2600(21)00435-5; html:https://europepmc.org/articles/PMC8523117 35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"

Background

High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.

Methods

We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.

Results

Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.

Conclusions

The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render +37434746,https://doi.org/10.1016/j.eclinm.2023.102077,"Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.","Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.",,EClinicalMedicine,2023,2023-06-29,Y,Pandemic; Healthcare Utilisation; Ethnic Differences,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).",,doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render 35308309,https://doi.org/10.1016/j.eclinm.2022.101346,"Healthcare workers' views on mandatory SARS-CoV-2 vaccination in the UK: A cross-sectional, mixed-methods analysis from the UK-REACH study.","Woolf K, Gogoi M, Martin CA, Papineni P, Lagrata S, Nellums LB, McManus IC, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Carr S, Tobin MD, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,EClinicalMedicine,2022,2022-03-15,Y,,,,"

Background

Several countries now have mandatory SARS-CoV-2 vaccination for healthcare workers (HCWs) or the general population. HCWs' views on this are largely unknown. Using data from the nationwide UK-REACH study we aimed to understand UK HCW's views on improving SARS-CoV-2 vaccination coverage, including mandatory vaccination.

Methods

Between 21st April and 26th June 2021, we administered an online questionnaire via email to 17 891 UK HCWs recruited as part of a longitudinal cohort from across the UK who had previously responded to a baseline questionnaire (primarily recruited through email) as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question ""What should society do if people do not get vaccinated against COVID-19?"" using qualitative content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not, using logistic regression to calculate its demographic predictors, and its occupational, health, and attitudinal predictors adjusted for demographics.

Findings

Of 5633 questionnaire respondents, 3235 answered the free text question. Median age of free text responders was 47 years (IQR 36-56) and 2705 (74.3%) were female. 18% (n = 578) favoured mandatory vaccination (201 [6%] participants for HCWs and others working with vulnerable populations; 377 [12%] for the general population), but the most frequent suggestion was education (32%, n = 1047). Older HCWs (OR 1.84; 95% CI 1.44-2.34 [≥55 years vs 16 years to <40 years]), HCWs vaccinated against influenza (OR 1.49; 95% CI 1.11-2.01 [2 vaccines vs none]), and with more positive vaccination attitudes generally (OR 1.10; 95% CI 1.06-1.15) were more likely to favour mandatory vaccination, whereas female HCWs (OR= 0.79, 95% CI 0.63-0.96, vs male HCWs) and Black HCWs (OR=0.46, 95% CI 0.25-0.85, vs white HCWs) were less likely to.

Interpretation

Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating, and supporting HCWs who are hesitant about vaccination may be more acceptable, effective, and equitable.

Funding

MRC-UK Research and Innovation grant (MR/V027549/1) and the Department of Health and Social Care (DHSC) via the National Institute for Health Research (NIHR). Core funding was also provided by NIHR Biomedical Research Centres.",,doi:https://doi.org/10.1016/j.eclinm.2022.101346; html:https://europepmc.org/articles/PMC8923694; pdf:https://europepmc.org/articles/PMC8923694?pdf=render 37192798,https://doi.org/10.1136/bmjopen-2022-066398,Impact of pausing elective hip and knee replacement surgery during winter 2017 on subsequent service provision at a major NHS Trust: a descriptive observational study using interrupted time series.,"Jones T, Penfold C, Redaniel MT, Eyles E, Keen T, Elliott A, Blom AW, Judge A.",,BMJ open,2023,2023-05-16,Y,Knee; Hip; Human Resource Management; Orthopaedic & Trauma Surgery,,,"

Objectives

To explore the impact of a temporary cancellation of elective surgery in winter 2017 on trends in primary hip and knee replacement at a major National Health Service (NHS) Trust, and whether lessons can be learnt about efficient surgery provision.

Design and setting

Observational descriptive study using interrupted time series analysis of hospital records to explore trends in primary hip and knee replacement surgery at a major NHS Trust, as well as patient characteristics, 2016-2019.

Intervention

A temporary cancellation of elective services for 2 months in winter 2017.

Outcomes

NHS-funded hospital admissions for primary hip or knee replacement, length of stay and bed occupancy. Additionally, we explored the ratio of elective to emergency admissions at the Trust as a measure of elective capacity, and the ratio of public to private provision of NHS-funded hip and knee surgery.

Results

After winter 2017, there was a sustained reduction in the number of knee replacements, a decrease in the proportion of most deprived people having knee replacements and an increase in average age for knee replacement and comorbidity for both types of surgery. The ratio of public to private provision dropped after winter 2017, and elective capacity generally has reduced over time. There was clear seasonality in provision of elective surgery, with less complex patients admitted during winter.

Conclusions

Declining elective capacity and seasonality has a marked effect on the provision of joint replacement, despite efficiency improvements in hospital treatment. The Trust has outsourced less complex patients to independent providers, and/or treated them during winter when capacity is most limited. There is a need to explore whether these are strategies that could be used explicitly to maximise the use of limited elective capacity, provide benefit to patients and value for money for taxpayers.",,doi:https://doi.org/10.1136/bmjopen-2022-066398; html:https://europepmc.org/articles/PMC10193088; pdf:https://europepmc.org/articles/PMC10193088?pdf=render 34732073,https://doi.org/10.1161/strokeaha.121.034787,"Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.","Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.",,Stroke,2021,2021-11-04,Y,Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19,,,"

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render +34340970,https://doi.org/10.3399/bjgp.2021.0301,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.,"Walker AJ, MacKenna B, Inglesby P, Tomlinson L, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19; Long Covid,,,"

Background

Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.

Aim

To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.

Design and setting

Population-based cohort study in English primary care.

Method

Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.

Results

Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).

Conclusion

Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.",,doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render PMC10464871,https://doi.org/,"A methodology to facilitate critical care research using multiple linked electronic, clinical and administrative health records at population scale","Griffiths R, Herbert L, Akbari A, Bailey R, Hollinghurst J, Pugh R, Szakmany T, Torabi F, Lyons R.",,International journal of population data science,,2023-08-31,Y,Intensive Care; Critical Care; Electronic Health Records; Icnarc; Linkable Research Data,,,"Abstract

Introduction

Critical Care is a specialty in medicine providing a service for severely ill and high-risk patients who, due to the nature of their condition, may require long periods recovering after discharge. Consequently, focus on the routine data collection carried out in Intensive Care Units (ICUs) leads to reporting that is confined to the critical care episode and is typically insensitive to variation in individual patient pathways through critical care to recovery. A resource which facilitates efficient research into interactions with healthcare services surrounding critical admissions, capturing the complete patient’s healthcare trajectory from primary care to non-acute hospital care prior to ICU, would provide an important longer-term perspective for critical care research.

Objective

To describe and apply a reproducible methodology that demonstrates how both routine administrative and clinically rich critical care data sources can be integrated with primary and secondary healthcare data to create a single dataset that captures a broader view of patient care.

Method

To demonstrate the INTEGRATE methodology, it was applied to routine administrative and clinical healthcare data sources in the Secure Anonymised Data Linking (SAIL) Databank to create a dataset of patients’ complete healthcare trajectory prior to critical care admission. SAIL is a national, data safe haven of anonymised linkable datasets about the population of Wales.

Results

When applying the INTEGRATE methodology in SAIL, between 2010 and 2019 we observed 91,582 critical admissions for 76,019 patients. Of these, 90,632 (99%) had an associated non-acute hospital admission, 48,979 (53%) had an emergency admission, and 64,832 (71%) a primary care interaction in the week prior to the critical care admission.

Conclusion

This methodology, at population scale, integrates two critical care data sources into a single dataset together with data sources on healthcare prior to critical admission, thus providing a key research asset to study critical care pathways.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464871/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464871/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10464871; pdf:https://europepmc.org/articles/PMC10464871?pdf=render 36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH). ,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render -34340970,https://doi.org/10.3399/bjgp.2021.0301,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.,"Walker AJ, MacKenna B, Inglesby P, Tomlinson L, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19; Long Covid,,,"

Background

Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.

Aim

To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.

Design and setting

Population-based cohort study in English primary care.

Method

Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.

Results

Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).

Conclusion

Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.",,doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render 35265823,https://doi.org/10.1016/j.eclinm.2022.101317,Variation in global COVID-19 symptoms by geography and by chronic disease: A global survey using the COVID-19 Symptom Mapper.,"Kadirvelu B, Burcea G, Quint JK, Costelloe CE, Faisal AA.",,EClinicalMedicine,2022,2022-03-06,Y,"Comorbidities; Pcr, Polymerase Chain Reaction; Covid-19; Covid-19 Symptoms; Covid Symptom Profile; Covid Symptoms Mapper; Covid Symptoms Survey; Covid-19, The Coronavirus Disease That First Appeared In 2019 Caused By The Sars-cov-2 Coronavirus.; Who, World Health Organization, A Specialized Agency Of The United Nations Responsible For International Public Health.",,,"

Background

COVID-19 is typically characterised by a triad of symptoms: cough, fever and loss of taste and smell, however, this varies globally. This study examines variations in COVID-19 symptom profiles based on underlying chronic disease and geographical location.

Methods

Using a global online symptom survey of 78,299 responders in 190 countries between 09/04/2020 and 22/09/2020, we conducted an exploratory study to examine symptom profiles associated with a positive COVID-19 test result by country and underlying chronic disease (single, co- or multi-morbidities) using statistical and machine learning methods.

Findings

From the results of 7980 COVID-19 tested positive responders, we find that symptom patterns differ by country. For example, India reported a lower proportion of headache (22.8% vs 47.8%, p<1e-13) and itchy eyes (7.3% vs. 16.5%, p=2e-8) than other countries. As with geographic location, we find people differed in their reported symptoms if they suffered from specific chronic diseases. For example, COVID-19 positive responders with asthma (25.3% vs. 13.7%, p=7e-6) were more likely to report shortness of breath compared to those with no underlying chronic disease.

Interpretation

We have identified variation in COVID-19 symptom profiles depending on geographic location and underlying chronic disease. Failure to reflect this symptom variation in public health messaging may contribute to asymptomatic COVID-19 spread and put patients with chronic diseases at a greater risk of infection. Future work should focus on symptom profile variation in the emerging variants of the SARS-CoV-2 virus. This is crucial to speed up clinical diagnosis, predict prognostic outcomes and target treatment.

Funding

We acknowledge funding to AAF by a UKRI Turing AI Fellowship and to CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, Asthma UK-British Lung Foundation, IQVIA, Chiesi AZ, and Insmed. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the Northwest London NIHR Applied Research Collaboration. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.",,doi:https://doi.org/10.1016/j.eclinm.2022.101317; html:https://europepmc.org/articles/PMC8898170; pdf:https://europepmc.org/articles/PMC8898170?pdf=render 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"

Objective

To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.

Design

Cross-sectional study.

Setting

East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.

Participants

EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.

Main outcome measure

COVID-19 incidence and mortality.

Results

Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).

Conclusions

In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render 33541353,https://doi.org/10.1186/s12916-020-01872-8,The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories.,"Liu Y, Morgenstern C, Kelly J, Lowe R, CMMID COVID-19 Working Group, Jit M.",,BMC medicine,2021,2021-02-05,Y,Quantitative; Pandemic; Health Impact Assessment; Public Health Intervention; Longitudinal Analysis; Policy Evaluation; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"

Background

Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories.

Methods

We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission using data from January to June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in Rt, levels of NPI intensity, time-varying changes in NPI effect, and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs.

Results

There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced Rt. Another three NPIs (workplace closure, income support, and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g. restrictions on 1000+ people gathering were not effective, restrictions on < 10 people gathering were). Evidence about the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Effect sizes varied depending on whether or not we included data after peak NPI intensity.

Conclusion

Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects, and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many, although not all, actions policy-makers are taking to respond to the COVID-19 pandemic.",,doi:https://doi.org/10.1186/s12916-020-01872-8; html:https://europepmc.org/articles/PMC7861967; pdf:https://europepmc.org/articles/PMC7861967?pdf=render 36498739,https://doi.org/10.3390/jcm11237163,Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis.,"Siddi S, Giné-Vázquez I, Bailon R, Matcham F, Lamers F, Kontaxis S, Laporta E, Garcia E, Arranz B, Dalla Costa G, Guerrero AI, Zabalza A, Buron MD, Comi G, Leocani L, Annas P, Hotopf M, Penninx BWJH, Magyari M, Sørensen PS, Montalban X, Lavelle G, Ivan A, Oetzmann C, White KM, Difrancesco S, Locatelli P, Mohr DC, Aguiló J, Narayan V, Folarin A, Dobson RJB, Dineley J, Leightley D, Cummins N, Vairavan S, Ranjan Y, Rashid Z, Rintala A, Girolamo G, Preti A, Simblett S, Wykes T, Pab Members, Myin-Germeys I, Haro JM, On Behalf Of The Radar-Cns Consortium.",,Journal of clinical medicine,2022,2022-12-01,Y,Stress; Heart rate; Multiple sclerosis; Physical Activity; Social Activity; Major Depressive Disorder; Depression Severity; Decentralized; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.",,doi:https://doi.org/10.3390/jcm11237163; html:https://europepmc.org/articles/PMC9738639; pdf:https://europepmc.org/articles/PMC9738639?pdf=render 33342219,https://doi.org/10.1161/circoutcomes.120.007085,Estimating the Effect of Reduced Attendance at Emergency Departments for Suspected Cardiac Conditions on Cardiac Mortality During the COVID-19 Pandemic.,"Katsoulis M, Gomes M, Lai AG, Henry A, Denaxas S, Lagiou P, Nafilyan V, Humberstone B, Banerjee A, Hemingway H, Lumbers RT.",,Circulation. Cardiovascular quality and outcomes,2021,2020-12-20,Y,"Cardiovascular diseases; Coronavirus; Pandemic; Heart Disease; Death, Sudden, Cardiac",,,,,doi:https://doi.org/10.1161/CIRCOUTCOMES.120.007085; html:https://europepmc.org/articles/PMC7819531; pdf:https://europepmc.org/articles/PMC7819531?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCOUTCOMES.120.007085 32220655,https://doi.org/10.1016/s2468-2667(20)30073-6,"The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study.","Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Jit M, Klepac P.",,The Lancet. Public health,2020,2020-03-25,Y,,,,"

Background

In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world.

Methods

To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April).

Findings

Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66-97) and 24% (13-90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic.

Interpretation

Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R0 and the duration of infectiousness.

Funding

Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.",,doi:https://doi.org/10.1016/S2468-2667(20)30073-6; html:https://europepmc.org/articles/PMC7158905; doi:https://doi.org/10.1016/s2468-2667(20)30073-6 -35235826,https://doi.org/10.1016/j.ijid.2022.02.051,"Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections - a survival analysis.","Hussey H, Davies MA, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Wasserman S, Boloko L, Symons G, Raubenheimer P, Parker A, Schrueder N, Solomon W, Rousseau P, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Boulle A, Hsiao NY.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2022,2022-02-27,Y,South Africa; Clinical Severity; Sars-cov-2; Omicron Variant; Rdrp Target Delay,,,"

Background

At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity.

Methods

RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection.

Results

A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.",,doi:https://doi.org/10.1016/j.ijid.2022.02.051; html:https://europepmc.org/articles/PMC8882068; pdf:https://europepmc.org/articles/PMC8882068?pdf=render 33939953,https://doi.org/10.1016/s0140-6736(21)00634-6,"Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.","Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, Eggo RM, Bhaskaran K, Wong AYS, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJW, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B, OpenSAFELY Collaborative.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,"

Background

COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

Methods

We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.

Findings

Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.

Interpretation

Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.

Funding

Medical Research Council.",,doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render +35235826,https://doi.org/10.1016/j.ijid.2022.02.051,"Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections - a survival analysis.","Hussey H, Davies MA, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Wasserman S, Boloko L, Symons G, Raubenheimer P, Parker A, Schrueder N, Solomon W, Rousseau P, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Boulle A, Hsiao NY.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2022,2022-02-27,Y,South Africa; Clinical Severity; Sars-cov-2; Omicron Variant; Rdrp Target Delay,,,"

Background

At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity.

Methods

RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection.

Results

A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.",,doi:https://doi.org/10.1016/j.ijid.2022.02.051; html:https://europepmc.org/articles/PMC8882068; pdf:https://europepmc.org/articles/PMC8882068?pdf=render 33031764,https://doi.org/10.1016/s0140-6736(20)32013-4,"Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2020,2020-10-05,Y,,,,"

Background

Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092).

Interpretation

In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19.

Funding

Medical Research Council and National Institute for Health Research.",,doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623 34328624,https://doi.org/10.1007/s11695-021-05493-9,30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.,"Singhal R, Ludwig C, Rudge G, Gkoutos GV, Tahrani A, Mahawar K, GENEVA Collaborators, Pędziwiatr M, Major P, Zarzycki P, Pantelis A, Lapatsanis DP, Stravodimos G, Matthys C, Focquet M, Vleeschouwers W, Spaventa AG, Zerrweck C, Vitiello A, Berardi G, Musella M, Sanchez-Meza A, Cantu FJ, Mora F, Cantu MA, Katakwar A, Reddy DN, Elmaleh H, Hassan M, Elghandour A, Elbanna M, Osman A, Khan A, Layani L, Kiran N, Velikorechin A, Solovyeva M, Melali H, Shahabi S, Agrawal A, Shrivastava A, Sharma A, Narwaria B, Narwaria M, Raziel A, Sakran N, Susmallian S, Karagöz L, Akbaba M, Pişkin SZ, Balta AZ, Senol Z, Manno E, Iovino MG, Osman A, Qassem M, Arana-Garza S, Povoas HP, Vilas-Boas ML, Naumann D, Super J, Li A, Ammori BJ, Balamoun H, Salman M, Nasta AM, Goel R, Sánchez-Aguilar H, Herrera MF, Abou-Mrad A, Cloix L, Mazzini GS, Kristem L, Lazaro A, Campos J, Bernardo J, González J, Trindade C, Viveiros O, Ribeiro R, Goitein D, Hazzan D, Segev L, Beck T, Reyes H, Monterrubio J, García P, Benois M, Kassir R, Contine A, Elshafei M, Aktas S, Weiner S, Heidsieck T, Level L, Pinango S, Ortega PM, Moncada R, Valenti V, Vlahović I, Boras Z, Liagre A, Martini F, Juglard G, Motwani M, Saggu SS, Al Moman H, López LAA, Cortez MAC, Zavala RA, D'Haese C, Kempeneers I, Himpens J, Lazzati A, Paolino L, Bathaei S, Bedirli A, Yavuz A, Büyükkasap Ç, Özaydın S, Kwiatkowski A, Bartosiak K, Walędziak M, Santonicola A, Angrisani L, Iovino P, Palma R, Iossa A, Boru CE, De Angelis F, Silecchia G, Hussain A, Balchandra S, Coltell IB, Pérez JL, Bohra A, Awan AK, Madhok B, Leeder PC, Awad S, Al-Khyatt W, Shoma A, Elghadban H, Ghareeb S, Mathews B, Kurian M, Larentzakis A, Vrakopoulou GZ, Albanopoulos K, Bozdag A, Lale A, Kirkil C, Dincer M, Bashir A, Haddad A, Hijleh LA, Zilberstein B, de Marchi DD, Souza WP, Brodén CM, Gislason H, Shah K, Ambrosi A, Pavone G, Tartaglia N, Kona SLK, Kalyan K, Perez CEG, Botero MAF, Covic A, Timofte D, Maxim M, Faraj D, Tseng L, Liem R, Ören G, Dilektasli E, Yalcin I, AlMukhtar H, Al Hadad M, Mohan R, Arora N, Bedi D, Rives-Lange C, Chevallier JM, Poghosyan T, Sebbag H, Zinaï L, Khaldi S, Mauchien C, Mazza D, Dinescu G, Rea B, Pérez-Galaz F, Zavala L, Besa A, Curell A, Balibrea JM, Vaz C, Galindo L, Silva N, Caballero JLE, Sebastian SO, Marchesini JCD, da Fonseca Pereira RA, Sobottka WH, Fiolo FE, Turchi M, Coelho ACJ, Zacaron AL, Barbosa A, Quinino R, Menaldi G, Paleari N, Martinez-Duartez P, de Aragon Ramírez de Esparza GM, Esteban VS, Torres A, Garcia-Galocha JL, Josa M, Pacheco-Garcia JM, Mayo-Ossorio MA, Chowbey P, Soni V, de Vasconcelos Cunha HA, Castilho MV, Ferreira RMA, Barreiro TA, Charalabopoulos A, Sdralis E, Davakis S, Bomans B, Dapri G, Van Belle K, Takieddine M, Vaneukem P, Karaca ESA, Karaca FC, Sumer A, Peksen C, Savas OA, Chousleb E, Elmokayed F, Fakhereldin I, Aboshanab HM, Swelium T, Gudal A, Gamloo L, Ugale A, Ugale S, Boeker C, Reetz C, Hakami IA, Mall J, Alexandrou A, Baili E, Bodnar Z, Maleckas A, Gudaityte R, Guldogan CE, Gundogdu E, Ozmen MM, Thakkar D, Dukkipati N, Shah PS, Shah SS, Shah SS, Adil MT, Jambulingam P, Mamidanna R, Whitelaw D, Adil MT, Jain V, Veetil DK, Wadhawan R, Torres A, Torres M, Tinoco T, Leclercq W, Romeijn M, van de Pas K, Alkhazraji AK, Taha SA, Ustun M, Yigit T, Inam A, Burhanulhaq M, Pazouki A, Eghbali F, Kermansaravi M, Jazi AHD, Mahmoudieh M, Mogharehabed N, Tsiotos G, Stamou K, Barrera Rodriguez FJ, Rojas Navarro MA, Torres OM, Martinez SL, Tamez ERM, Millan Cornejo GA, Flores JEG, Mohammed DA, Elfawal MH, Shabbir A, Guowei K, So JB, Kaplan ET, Kaplan M, Kaplan T, Pham D, Rana G, Kappus M, Gadani R, Kahitan M, Pokharel K, Osborne A, Pournaras D, Hewes J, Napolitano E, Chiappetta S, Bottino V, Dorado E, Schoettler A, Gaertner D, Fedtke K, Aguilar-Espinosa F, Aceves-Lozano S, Balani A, Nagliati C, Pennisi D, Rizzi A, Frattini F, Foschi D, Benuzzi L, Parikh C, Shah H, Pinotti E, Montuori M, Borrelli V, Dargent J, Copaescu CA, Hutopila I, Smeu B, Witteman B, Hazebroek E, Deden L, Heusschen L, Okkema S, Aufenacker T, den Hengst W, Vening W, van der Burgh Y, Ghazal A, Ibrahim H, Niazi M, Alkhaffaf B, Altarawni M, Cesana GC, Anselmino M, Uccelli M, Olmi S, Stier C, Akmanlar T, Sonnenberg T, Schieferbein U, Marcolini A, Awruch D, Vicentin M, de Souza Bastos EL, Gregorio SA, Ahuja A, Mittal T, Bolckmans R, Wiggins T, Baratte C, Wisnewsky JA, Genser L, Chong L, Taylor L, Ward S, Chong L, Taylor L, Hi MW, Heneghan H, Fearon N, Plamper A, Rheinwalt K, Heneghan H, Geoghegan J, Ng KC, Fearon N, Kaseja K, Kotowski M, Samarkandy TA, Leyva-Alvizo A, Corzo-Culebro L, Wang C, Yang W, Dong Z, Riera M, Jain R, Hamed H, Said M, Zarzar K, Garcia M, Türkçapar AG, Şen O, Baldini E, Conti L, Wietzycoski C, Lopes E, Pintar T, Salobir J, Aydin C, Atici SD, Ergin A, Ciyiltepe H, Bozkurt MA, Kizilkaya MC, Onalan NBD, Zuber MNBA, Wong WJ, Garcia A, Vidal L, Beisani M, Pasquier J, Vilallonga R, Sharma S, Parmar C, Lee L, Sufi P, Sinan H, Saydam M.",,Obesity surgery,2021,2021-07-30,Y,Pandemic; Obesity Surgery; Bariatric Surgery; Revisional Surgery; Covid-19; Sars-cov-2,,,"

Background

There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates.

Methods

We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020.

Results

Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country.

Conclusions

BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak.",,doi:https://doi.org/10.1007/s11695-021-05493-9; html:https://europepmc.org/articles/PMC8323543; pdf:https://europepmc.org/articles/PMC8323543?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s11695-021-05493-9.pdf 33200120,https://doi.org/10.1016/j.eclinm.2020.100630,Ethnicity and clinical outcomes in COVID-19: A systematic review and meta-analysis.,"Sze S, Pan D, Nevill CR, Gray LJ, Martin CA, Nazareth J, Minhas JS, Divall P, Khunti K, Abrams KR, Nellums LB, Pareek M.",,EClinicalMedicine,2020,2020-11-12,Y,Infection; Transmission; RACE; Death; Ethnicity; Outcome; Asian; Hispanic; Ethnic; Sars-cov-2; Covid-19 Black; Disporportionate; Itu Admission,,,"

Background

Patients from ethnic minority groups are disproportionately affected by Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis to explore the relationship between ethnicity and clinical outcomes in COVID-19.

Methods

Databases (MEDLINE, EMBASE, PROSPERO, Cochrane library and MedRxiv) were searched up to 31st August 2020, for studies reporting COVID-19 data disaggregated by ethnicity. Outcomes were: risk of infection; intensive therapy unit (ITU) admission and death. PROSPERO ID: 180654.

Findings

18,728,893 patients from 50 studies were included; 26 were peer-reviewed; 42 were from the United States of America and 8 from the United Kingdom. Individuals from Black and Asian ethnicities had a higher risk of COVID-19 infection compared to White individuals. This was consistent in both the main analysis (pooled adjusted RR for Black: 2.02, 95% CI 1.67-2.44; pooled adjusted RR for Asian: 1.50, 95% CI 1.24-1.83) and sensitivity analyses examining peer-reviewed studies only (pooled adjusted RR for Black: 1.85, 95%CI: 1.46-2.35; pooled adjusted RR for Asian: 1.51, 95% CI 1.22-1.88). Individuals of Asian ethnicity may also be at higher risk of ITU admission (pooled adjusted RR 1.97 95% CI 1.34-2.89) (but no studies had yet been peer-reviewed) and death (pooled adjusted RR/HR 1.22 [0.99-1.50]).

Interpretation

Individuals of Black and Asian ethnicity are at increased risk of COVID-19 infection compared to White individuals; Asians may be at higher risk of ITU admission and death. These findings are of critical public health importance in informing interventions to reduce morbidity and mortality amongst ethnic minority groups.",,doi:https://doi.org/10.1016/j.eclinm.2020.100630; html:https://europepmc.org/articles/PMC7658622; pdf:https://europepmc.org/articles/PMC7658622?pdf=render 34089614,https://doi.org/10.1093/ije/dyab028,Cohort Profile: Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) Database.,"Mulholland RH, Vasileiou E, Simpson CR, Robertson C, Ritchie LD, Agrawal U, Woolhouse M, Murray JL, Stagg HR, Docherty AB, McCowan C, Wood R, Stock SJ, Sheikh A.",,International journal of epidemiology,2021,2021-08-01,Y,,,,,,doi:https://doi.org/10.1093/ije/dyab028; html:https://europepmc.org/articles/PMC8195245; pdf:https://europepmc.org/articles/PMC8195245?pdf=render 34190735,https://doi.org/,The changing characteristics of COVID-19 presentations. A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave.,"Atkin C, Kamwa V, Reddy-Kolanu V, Parekh D, Evison F, Nightingale P, Gallier S, Ball S, Sapey E.",,Acute medicine,2021,2021-01-01,N,,,,"

Background

This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus.

Methods

All patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days.

Results

Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions.

Conclusion

Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.",, -35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,doi:https://doi.org/10.1093/intqhc/mzac031 33993870,https://doi.org/10.1186/s12916-021-02000-w,Impact of COVID-19 lockdown on the incidence and mortality of acute exacerbations of chronic obstructive pulmonary disease: national interrupted time series analyses for Scotland and Wales.,"Alsallakh MA, Sivakumaran S, Kennedy S, Vasileiou E, Lyons RA, Robertson C, Sheikh A, Davies GA, EAVE II Collaborators.",,BMC medicine,2021,2021-05-17,Y,Acute Exacerbation Of Chronic Obstructive Pulmonary Disease; Covid-19 Lockdown,,,"

Background

The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic's impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments.

Methods

Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years. For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations.

Results

Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages. There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33). In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81).

Conclusions

The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths. This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.",,doi:https://doi.org/10.1186/s12916-021-02000-w; html:https://europepmc.org/articles/PMC8126470; pdf:https://europepmc.org/articles/PMC8126470?pdf=render +35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,doi:https://doi.org/10.1093/intqhc/mzac031 33082154,https://doi.org/10.1136/bmj.m3731,Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study.,"Clift AK, Coupland CAC, Keogh RH, Diaz-Ordaz K, Williamson E, Harrison EM, Hayward A, Hemingway H, Horby P, Mehta N, Benger J, Khunti K, Spiegelhalter D, Sheikh A, Valabhji J, Lyons RA, Robson J, Semple MG, Kee F, Johnson P, Jebb S, Williams T, Hippisley-Cox J.",,BMJ (Clinical research ed.),2020,2020-10-20,Y,,,,"

Objective

To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults.

Design

Population based cohort study.

Setting and participants

QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020.

Main outcome measures

The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period.

Results

4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R2); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell's C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19.

Conclusion

The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves.",,doi:https://doi.org/10.1136/bmj.m3731; html:https://europepmc.org/articles/PMC7574532; pdf:https://europepmc.org/articles/PMC7574532?pdf=render 33085509,https://doi.org/10.7326/m20-4986,COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study of 8 Million Adults.,"Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J.",,Annals of internal medicine,2021,2020-10-21,Y,,,,,,doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?pdf=render 35896970,https://doi.org/10.1186/s12879-022-07628-4,SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2.,"Eales O, Page AJ, de Oliveira Martins L, Wang H, Bodinier B, Haw D, Jonnerby J, Atchison C, COVID-19 Genomics UK (COG-UK) Consortium, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Chadeau-Hyam M, Donnelly CA, Elliott P.",,BMC infectious diseases,2022,2022-07-27,Y,Mutation; Genetic diversity; Transmission Advantage; Covid-19; Sars-cov-2; Delta Variant,,,"

Background

Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape.

Methods

We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September-27 September 2021) and 15 (19 October-5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.

Results

We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.

Conclusions

As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.",,doi:https://doi.org/10.1186/s12879-022-07628-4; html:https://europepmc.org/articles/PMC9326417; pdf:https://europepmc.org/articles/PMC9326417?pdf=render @@ -305,7 +305,7 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 34784292,https://doi.org/10.2196/32587,Investigating the Use of Digital Health Technology to Monitor COVID-19 and Its Effects: Protocol for an Observational Study (Covid Collab Study).,"Stewart C, Ranjan Y, Conde P, Rashid Z, Sankesara H, Bai X, Dobson RJB, Folarin AA.",,JMIR research protocols,2021,2021-12-08,Y,Monitoring; Infectious disease; Recovery; Mobile phone; Feasibility; Surveillance; Data; Mental health; Observational; Smartphone; Wearable; Mobile Health; Wearable Devices; Digital Health; Crowdsourced; Covid-19,,,"

Background

The ubiquity of mobile phones and increasing use of wearable fitness trackers offer a wide-ranging window into people's health and well-being. There are clear advantages in using remote monitoring technologies to gain an insight into health, particularly under the shadow of the COVID-19 pandemic.

Objective

Covid Collab is a crowdsourced study that was set up to investigate the feasibility of identifying, monitoring, and understanding the stratification of SARS-CoV-2 infection and recovery through remote monitoring technologies. Additionally, we will assess the impacts of the COVID-19 pandemic and associated social measures on people's behavior, physical health, and mental well-being.

Methods

Participants will remotely enroll in the study through the Mass Science app to donate historic and prospective mobile phone data, fitness tracking wearable data, and regular COVID-19-related and mental health-related survey data. The data collection period will cover a continuous period (ie, both before and after any reported infections), so that comparisons to a participant's own baseline can be made. We plan to carry out analyses in several areas, which will cover symptomatology; risk factors; the machine learning-based classification of illness; and trajectories of recovery, mental well-being, and activity.

Results

As of June 2021, there are over 17,000 participants-largely from the United Kingdom-and enrollment is ongoing.

Conclusions

This paper introduces a crowdsourced study that will include remotely enrolled participants to record mobile health data throughout the COVID-19 pandemic. The data collected may help researchers investigate a variety of areas, including COVID-19 progression; mental well-being during the pandemic; and the adherence of remote, digitally enrolled participants.

International registered report identifier (irrid)

DERR1-10.2196/32587.",,doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240 37253531,https://doi.org/10.1136/bmjgh-2022-009997,Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.,"Batista-da-Silva AA, Moraes CB, Bozza HR, Bastos LDSL, Ranzani OT, Hamacher S, Bozza FA, Comitê Gestor Conexão Saúde.",,BMJ global health,2023,2023-05-01,Y,"Control strategies; Public Health; Intervention Study; Infections, Diseases, Disorders, Injuries; Covid-19",,,"

Introduction

Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil.

Methods

We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré.

Results

Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset.

Conclusion

An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.",,doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render 37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render -34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render +34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render; pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf 35144240,https://doi.org/10.2196/32543,Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.,"Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",,JMIR public health and surveillance,2022,2022-05-27,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"

Background

The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.

Objective

We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.

Methods

We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.

Results

Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.

Conclusions

The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",,doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729 36820079,https://doi.org/10.1183/23120541.00274-2022,Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.,"Daines L, Zheng B, Elneima O, Harrison E, Lone NI, Hurst JR, Brown JS, Sapey E, Chalmers JD, Quint JK, Pfeffer P, Siddiqui S, Walker S, Poinasamy K, McAuley H, Sereno M, Shikotra A, Singapuri A, Docherty AB, Marks M, Toshner M, Howard LS, Horsley A, Jenkins G, Porter JC, Ho LP, Raman B, Wain LV, Brightling CE, Evans RA, Heaney LG, De Soyza A, Sheikh A.",,ERJ open research,2023,2023-01-01,Y,,,,"

Background

Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.

Methods

PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.

Results

We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21).

Conclusions

Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.",,doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?pdf=render 35909058,https://doi.org/10.1016/s2589-7500(22)00123-6,Remote COVID-19 Assessment in Primary Care (RECAP) risk prediction tool: derivation and real-world validation studies.,"Espinosa-Gonzalez A, Prociuk D, Fiorentino F, Ramtale C, Mi E, Mi E, Glampson B, Neves AL, Okusi C, Husain L, Macartney J, Brown M, Browne B, Warren C, Chowla R, Heaversedge J, Greenhalgh T, de Lusignan S, Mayer E, Delaney BC.",,The Lancet. Digital health,2022,2022-07-28,Y,,,,"

Background

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO2]) and RECAP-oxygen saturation score (RECAP-O2; with SpO2).

Methods

RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people.

Findings

Data were available from 8311 individuals. Observations, such as SpO2, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO2 was available for 1364 (70·0%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0·80 (95% CI 0·76-0·85) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98·1-99·2; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO2 at rest (as a percentage); the area under the curve was 0·84 (0·78-0·90) and on validation the negative predictive value of low risk designation was 99% (95% CI 98·9-99·7; 1176 of 1183).

Interpretation

Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO2 is available, RECAP-O2 is useful to assess the need for treatment escalation.

Funding

Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.",,doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render @@ -332,8 +332,8 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 33087383,https://doi.org/10.1136/bmjopen-2020-043010,Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions. ,"Lyons J, Akbari A, Torabi F, Davies GI, North L, Griffiths R, Bailey R, Hollinghurst J, Fry R, Turner SL, Thompson D, Rafferty J, Mizen A, Orton C, Thompson S, Au-Yeung L, Cross L, Gravenor MB, Brophy S, Lucini B, John A, Szakmany T, Davies J, Davies C, Thomas DR, Williams C, Emmerson C, Cottrell S, Connor TR, Taylor C, Pugh RJ, Diggle P, John G, Scourfield S, Hunt J, Cunningham AM, Helliwell K, Lyons R.",,BMJ open,2020,2020-10-21,Y,,,,"The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions. Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection. The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?pdf=render 35022215,https://doi.org/10.1136/bmj-2021-067519,Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.,"Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.",,BMJ (Clinical research ed.),2022,2022-01-12,Y,,,,"

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.",,doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render -37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"

Purpose

People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.

Methods

We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.

Results

There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.

Conclusions

COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render 34862222,https://doi.org/10.7861/clinmed.2021-0386,'What is the risk to me from COVID-19?': Public involvement in providing mortality risk information for people with 'high-risk' conditions for COVID-19 (OurRisk.CoV).,"Banerjee A, Pasea L, Manohar S, Lai AG, Hemingway E, Sofer I, Katsoulis M, Sood H, Morris A, Cake C, Fitzpatrick NK, Williams B, Denaxas S, Hemingway H, and members of the Health Data Research UK COVID-19 Patient and Public Involvement and Engagement Panel.",,"Clinical medicine (London, England)",2021,2021-11-01,N,Mortality; Coronavirus; Patient And Public Involvement; Risk Information,,,"Patients and public have sought mortality risk information throughout the pandemic, but their needs may not be served by current risk prediction tools. Our mixed methods study involved: (1) systematic review of published risk tools for prognosis, (2) provision and patient testing of new mortality risk estimates for people with high-risk conditions and (3) iterative patient and public involvement and engagement with qualitative analysis. Only one of 53 (2%) previously published risk tools involved patients or the public, while 11/53 (21%) had publicly accessible portals, but all for use by clinicians and researchers.Among people with a wide range of underlying conditions, there has been sustained interest and engagement in accessible and tailored, pre- and postpandemic mortality information. Informed by patient feedback, we provide such information in 'five clicks' (https://covid19-phenomics.org/OurRiskCoV.html), as context for decision making and discussions with health professionals and family members. Further development requires curation and regular updating of NHS data and wider patient and public engagement.",,doi:https://doi.org/10.7861/clinmed.2021-0386; html:https://europepmc.org/articles/PMC8806292; pdf:https://europepmc.org/articles/PMC8806292?pdf=render; doi:https://doi.org/10.7861/clinmed.2021-0386 +37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"

Purpose

People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.

Methods

We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.

Results

There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.

Conclusions

COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render 34192199,https://doi.org/10.1136/bmjpo-2021-001049,Staff-pupil SARS-CoV-2 infection pathways in schools in Wales: a population-level linked data approach.,"Thompson DA, Abbasizanjani H, Fry R, Marchant E, Griffiths L, Akbari A, Hollinghurst J, North L, Lyons J, Torabi F, Davies G, Gravenor MB, Lyons RA.",,BMJ paediatrics open,2021,2021-05-10,Y,Disease transmission; Schools; Public Health; Sars-cov-2,,,"

Background

Better understanding of the role that children and school staff play in the transmission of SARS-CoV-2 is essential to guide policy development on controlling infection while minimising disruption to children's education and well-being.

Methods

Our national e-cohort (n=464531) study used anonymised linked data for pupils, staff and associated households linked via educational settings in Wales. We estimated the odds of testing positive for SARS-CoV-2 infection for staff and pupils over the period August- December 2020, dependent on measures of recent exposure to known cases linked to their educational settings.

Results

The total number of cases in a school was not associated with a subsequent increase in the odds of testing positive (staff OR per case: 0.92, 95% CI 0.85 to 1.00; pupil OR per case: 0.98, 95% CI 0.93 to 1.02). Among pupils, the number of recent cases within the same year group was significantly associated with subsequent increased odds of testing positive (OR per case: 1.12, 95% CI 1.08 to 1.15). These effects were adjusted for a range of demographic covariates, and in particular any known cases within the same household, which had the strongest association with testing positive (staff OR: 39.86, 95% CI 35.01 to 45.38; pupil OR: 9.39, 95% CI 8.94 to 9.88).

Conclusions

In a national school cohort, the odds of staff testing positive for SARS-CoV-2 infection were not significantly increased in the 14-day period after case detection in the school. However, pupils were found to be at increased odds, following cases appearing within their own year group, where most of their contacts occur. Strong mitigation measures over the whole of the study period may have reduced wider spread within the school environment.",,doi:https://doi.org/10.1136/bmjpo-2021-001049; html:https://europepmc.org/articles/PMC8111870; pdf:https://europepmc.org/articles/PMC8111870?pdf=render 35448463,https://doi.org/10.3390/metabo12040276,MetaboListem and TABoLiSTM: Two Deep Learning Algorithms for Metabolite Named Entity Recognition.,"Yeung CS, Beck T, Posma JM.",,Metabolites,2022,2022-03-22,Y,Natural Language Processing; Named Entity Recognition; Deep Learning,,,"Reviewing the metabolomics literature is becoming increasingly difficult because of the rapid expansion of relevant journal literature. Text-mining technologies are therefore needed to facilitate more efficient literature reviews. Here we contribute a standardised corpus of full-text publications from metabolomics studies and describe the development of two metabolite named entity recognition (NER) methods. These methods are based on Bidirectional Long Short-Term Memory (BiLSTM) networks and each incorporate different transfer learning techniques (for tokenisation and word embedding). Our first model (MetaboListem) follows prior methodology using GloVe word embeddings. Our second model exploits BERT and BioBERT for embedding and is named TABoLiSTM (Transformer-Affixed BiLSTM). The methods are trained on a novel corpus annotated using rule-based methods, and evaluated on manually annotated metabolomics articles. MetaboListem (F1-score 0.890, precision 0.892, recall 0.888) and TABoLiSTM (BioBERT version: F1-score 0.909, precision 0.926, recall 0.893) have achieved state-of-the-art performance on metabolite NER. A training corpus with full-text sentences from >1000 full-text Open Access metabolomics publications with 105,335 annotated metabolites was created, as well as a manually annotated test corpus (19,138 annotations). This work demonstrates that deep learning algorithms are capable of identifying metabolite names accurately and efficiently in text. The proposed corpus and NER algorithms can be used for metabolomics text-mining tasks such as information retrieval, document classification and literature-based discovery and are available from the omicsNLP GitHub repository.",,doi:https://doi.org/10.3390/metabo12040276; html:https://europepmc.org/articles/PMC9031427; pdf:https://europepmc.org/articles/PMC9031427?pdf=render 35184736,https://doi.org/10.1186/s12916-022-02271-x,Comparative assessment of methods for short-term forecasts of COVID-19 hospital admissions in England at the local level.,"Meakin S, Abbott S, Bosse N, Munday J, Gruson H, Hellewell J, Sherratt K, CMMID COVID-19 Working Group, Funk S.",,BMC medicine,2022,2022-02-21,Y,Forecasting; Infectious disease; outbreak; Real-time; Ensemble; Healthcare Demand; Covid-19,,,"

Background

Forecasting healthcare demand is essential in epidemic settings, both to inform situational awareness and facilitate resource planning. Ideally, forecasts should be robust across time and locations. During the COVID-19 pandemic in England, it is an ongoing concern that demand for hospital care for COVID-19 patients in England will exceed available resources.

Methods

We made weekly forecasts of daily COVID-19 hospital admissions for National Health Service (NHS) Trusts in England between August 2020 and April 2021 using three disease-agnostic forecasting models: a mean ensemble of autoregressive time series models, a linear regression model with 7-day-lagged local cases as a predictor, and a scaled convolution of local cases and a delay distribution. We compared their point and probabilistic accuracy to a mean-ensemble of them all and to a simple baseline model of no change from the last day of admissions. We measured predictive performance using the weighted interval score (WIS) and considered how this changed in different scenarios (the length of the predictive horizon, the date on which the forecast was made, and by location), as well as how much admissions forecasts improved when future cases were known.

Results

All models outperformed the baseline in the majority of scenarios. Forecasting accuracy varied by forecast date and location, depending on the trajectory of the outbreak, and all individual models had instances where they were the top- or bottom-ranked model. Forecasts produced by the mean-ensemble were both the most accurate and most consistently accurate forecasts amongst all the models considered. Forecasting accuracy was improved when using future observed, rather than forecast, cases, especially at longer forecast horizons.

Conclusions

Assuming no change in current admissions is rarely better than including at least a trend. Using confirmed COVID-19 cases as a predictor can improve admissions forecasts in some scenarios, but this is variable and depends on the ability to make consistently good case forecasts. However, ensemble forecasts can make forecasts that make consistently more accurate forecasts across time and locations. Given minimal requirements on data and computation, our admissions forecasting ensemble could be used to anticipate healthcare needs in future epidemic or pandemic settings.",,doi:https://doi.org/10.1186/s12916-022-02271-x; html:https://europepmc.org/articles/PMC8858706; pdf:https://europepmc.org/articles/PMC8858706?pdf=render @@ -358,8 +358,8 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 33758017,https://doi.org/10.1126/science.abf9648,The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia.,"Pavelka M, Van-Zandvoort K, Abbott S, Sherratt K, Majdan M, CMMID COVID-19 working group, Inštitút Zdravotných Analýz, Jarčuška P, Krajčí M, Flasche S, Funk S.",,"Science (New York, N.Y.)",2021,2021-03-23,Y,,,,"Slovakia conducted multiple rounds of population-wide rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% confidence interval: 57 to 58%) within 1 week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1 to 6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared with a scenario of unmitigated growth was 70% (67 to 73%). Modeling indicated that this decrease could not be explained solely by infection control measures but required the addition of the isolation and quarantine of household members of those testing positive.",,doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render 33316211,https://doi.org/10.1016/s2352-3018(20)30305-2,HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform.,"Bhaskaran K, Rentsch CT, MacKenna B, Schultze A, Mehrkar A, Bates CJ, Eggo RM, Morton CE, Bacon SCJ, Inglesby P, Douglas IJ, Walker AJ, McDonald HI, Cockburn J, Williamson EJ, Evans D, Forbes HJ, Curtis HJ, Hulme WJ, Parry J, Hester F, Harper S, Evans SJW, Smeeth L, Goldacre B.",,The lancet. HIV,2021,2020-12-11,Y,,,,"

Background

Whether HIV infection is associated with risk of death due to COVID-19 is unclear. We aimed to investigate this association in a large-scale population-based study in England.

Methods

We did a retrospective cohort study. Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. We included all adults (aged ≥18 years) alive and in follow-up on Feb 1, 2020, and with at least 1 year of continuous registration with a general practitioner before this date. People with a primary care record for HIV infection were compared with people without HIV. The outcome was COVID-19 death, defined as the presence of International Classification of Diseases 10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death; they were initially adjusted for age and sex, then we added adjustment for index of multiple deprivation and ethnicity, and then for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities, and calendar time.

Results

17 282 905 adults were included, of whom 27 480 (0·16%) had HIV recorded. People living with HIV were more likely to be male, of Black ethnicity, and from a more deprived geographical area than the general population. 14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV. People living with HIV had higher risk of COVID-19 death than those without HIV after adjusting for age and sex: hazard ratio (HR) 2·90 (95% CI 1·96-4·30; p<0·0001). The association was attenuated, but risk remained high, after adjustment for deprivation, ethnicity, smoking and obesity: adjusted HR 2·59 (95% CI 1·74-3·84; p<0·0001). There was some evidence that the association was larger among people of Black ethnicity: HR 4·31 (95% CI 2·42-7·65) versus 1·84 (1·03-3·26) in non-Black individuals (p-interaction=0·044).

Interpretation

People with HIV in the UK seem to be at increased risk of COVID-19 mortality. Targeted policies should be considered to address this raised risk as the pandemic response evolves.

Funding

Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.",,doi:https://doi.org/10.1016/S2352-3018(20)30305-2; html:https://europepmc.org/articles/PMC7773630; pdf:https://europepmc.org/articles/PMC7773630?pdf=render 33667930,https://doi.org/10.1016/j.ijmedinf.2021.104400,Real-time spatial health surveillance: Mapping the UK COVID-19 epidemic.,"Fry R, Hollinghurst J, Stagg HR, Thompson DA, Fronterre C, Orton C, Lyons RA, Ford DV, Sheikh A, Diggle PJ.",,International journal of medical informatics,2021,2021-01-28,Y,,,,"Introduction The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Objectives The primary objective of this study was to develop a real-time geospatial surveillance system to monitor the spread of COVID-19 across the UK. Methods Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. Results We demonstrate that using a combination of crowd-sourced app data and sophisticated geo-statistical techniques it is possible to predict hot spots of COVID-19 at fine geographic scales, nationally. We are also able to produce estimates of their precision, which is an important pre-requisite to an effective control strategy to guard against over-reaction to potentially spurious features of 'best guess' predictions. Conclusion In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.",,doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148 -37248229,https://doi.org/10.1038/s41467-023-38756-3,Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics.,"Gao J, Heintz J, Mack C, Glass L, Cross A, Sun J.",,Nature communications,2023,2023-05-29,Y,,,,"In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 [Formula: see text] and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.",,doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render; doi:https://doi.org/10.1038/s41467-023-38756-3 33419870,https://doi.org/10.1136/bmjhci-2020-100254,Network graph representation of COVID-19 scientific publications to aid knowledge discovery. ,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,BMJ health & care informatics,2021,2021-01-01,Y,,,,"Numerous scientific journal articles related to COVID-19 have been rapidly published, making navigation and understanding of relationships difficult. A graph network was constructed from the publicly available COVID-19 Open Research Dataset (CORD-19) of COVID-19-related publications using an engine leveraging medical knowledge bases to identify discrete medical concepts and an open-source tool (Gephi) to visualise the network. The network shows connections between diseases, medications and procedures identified from the title and abstract of 195 958 COVID-19-related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledge base and the size of the node related to the number of publications containing the term. The data set and visualisations were made publicly accessible via a webtool. Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity inter-relationships to improve understanding of diseases such as COVID-19.",,doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render +37248229,https://doi.org/10.1038/s41467-023-38756-3,Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics.,"Gao J, Heintz J, Mack C, Glass L, Cross A, Sun J.",,Nature communications,2023,2023-05-29,Y,,,,"In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 [Formula: see text] and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.",,doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render; doi:https://doi.org/10.1038/s41467-023-38756-3 35962974,https://doi.org/10.1093/ije/dyac158,Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform.,"Wing K, Grint DJ, Mathur R, Gibbs HP, Hickman G, Nightingale E, Schultze A, Forbes H, Nafilyan V, Bhaskaran K, Williamson E, House T, Pellis L, Herrett E, Gautam N, Curtis HJ, Rentsch CT, Wong AYS, MacKenna B, Mehrkar A, Bacon S, Douglas IJ, Evans SJW, Tomlinson L, Goldacre B, Eggo RM.",,International journal of epidemiology,2022,2022-12-01,Y,Household; Older People; Ethnicity; Deprivation; Comorbidities; Multigenerational; Population-level; Covid-19; Opensafely,,,"

Background

Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older individuals.

Methods

With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of age-based generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in Wave 1 (1 February 2020-31 August 2020) and 2 731 427 in Wave 2 (1 September 2020-31 January 2021).

Results

Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves [e.g. Wave 2, 67+ living with three other generations vs 67+-year-olds only: White hazard ratio (HR) 1.61 95% CI 1.38-1.87, South Asian HR 1.76 95% CI 1.48-2.10], with a trend for increased risks of severe COVID-19 with increasing generations in Wave 2. There was also an increased risk of severe COVID-19 in Wave 1 associated with living alone for White (HR 1.35 95% CI 1.30-1.41), South Asian (HR 1.47 95% CI 1.18-1.84) and Other (HR 1.72 95% CI 0.99-2.97) ethnicities, an effect that persisted for White older people in Wave 2.

Conclusions

Both multigenerational living and living alone were associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings, whereas a substantial proportion of White older people live alone. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics.",,doi:https://doi.org/10.1093/ije/dyac158; html:https://europepmc.org/articles/PMC9384728; pdf:https://europepmc.org/articles/PMC9384728?pdf=render 36992188,https://doi.org/10.3390/vaccines11030604,"Household Composition and Inequalities in COVID-19 Vaccination in Wales, UK.","Lench A, Perry M, Johnson RD, Fry R, Richardson G, Lyons RA, Akbari A, Edwards A, Collins B, Joseph-Williams N, Cooper A, Cottrell S.",,Vaccines,2023,2023-03-07,Y,Vaccines; Vaccination; Households; Inequalities; Immunisation; Household Composition; Inequities; Covid-19,,,"The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43-0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.",,doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render 36982069,https://doi.org/10.3390/ijerph20065161,The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.,"Lavalle R, Condominas E, Haro JM, Giné-Vázquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Peñarrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.",,International journal of environmental research and public health,2023,2023-03-15,Y,Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study,,,"The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the ""new normality"", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.",,doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render @@ -379,7 +379,7 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 33995410,https://doi.org/10.3389/fimmu.2021.671052,Plasma Lectin Pathway Complement Proteins in Patients With COVID-19 and Renal Disease.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Gisby J, Clarke CL, Prendecki M, McAdoo SP, Sandhu E, Lightstone L, Thomas DC, Willicombe M, Botto M, Peters JE, Pickering MC, Thiel S.",,Frontiers in immunology,2021,2021-04-29,Y,Complement; Lectin; Coronavirus; Chronic Kidney Disease; Covid-19,,,"We do not understand why non-white ethnicity and chronic kidney disease increase susceptibility to COVID-19. The lectin pathway of complement activation is a key contributor to innate immunity and inflammation. Concentrations of plasma lectin pathway proteins influence pathway activity and vary with ethnicity. We measured circulating lectin proteins in a multi-ethnic cohort of chronic kidney disease patients with and without COVID19 infection to determine if lectin pathway activation was contributing to COVID19 severity. We measured 11 lectin proteins in serial samples from a cohort of 33 patients with chronic kidney impairment and COVID19. Controls were single plasma samples from 32 patients on dialysis and 32 healthy individuals. We demonstrated multiple associations between recognition molecules and associated proteases of the lectin pathway and COVID-19, including COVID-19 severity. Some of these associations were unique to patients of Asian and White ethnicity. Our novel findings demonstrate that COVID19 infection alters the concentration of plasma lectin proteins and some of these changes were linked to ethnicity. This suggests a role for the lectin pathway in the host response to COVID-19 and suggest that variability within this pathway may contribute to ethnicity-associated differences in susceptibility to severe COVID-19.",,doi:https://doi.org/10.3389/fimmu.2021.671052; html:https://europepmc.org/articles/PMC8118695; pdf:https://europepmc.org/articles/PMC8118695?pdf=render 36962513,https://doi.org/10.1371/journal.pgph.0000502,"Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.","Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitjà O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.",,PLOS global public health,2022,2022-09-13,Y,,,,"Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.",,doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render 36315390,https://doi.org/10.1002/eat.23834,"Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.","Davies HL, Hübel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",,The International journal of eating disorders,2023,2022-10-31,Y,Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation,,,"

Objective

The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.

Method

Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.

Results

Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.

Discussion

Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.

Public significance

In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",,doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render -33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.

Results

We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render +33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.

Results

We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render; pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf 35983770,https://doi.org/10.2807/1560-7917.es.2022.27.33.2100885,"Recording of 'COVID-19 vaccine declined': a cohort study on 57.9 million National Health Service patients' records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021.","Curtis HJ, Inglesby P, MacKenna B, Croker R, Hulme WJ, Rentsch CT, Bhaskaran K, Mathur R, Morton CE, Bacon SC, Smith RM, Evans D, Mehrkar A, Tomlinson L, Walker AJ, Bates C, Hickman G, Ward T, Morley J, Cockburn J, Davy S, Williamson EJ, Eggo RM, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2022,2022-08-01,Y,Vaccination; Vaccine Hesitancy; Nhs England; Covid-19; Sars-cov-2,,,"BackgroundPriority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.AimWe describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.MethodsWith the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or 'at risk'. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.ResultsOf 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.",,doi:https://doi.org/10.2807/1560-7917.ES.2022.27.33.2100885; html:https://europepmc.org/articles/PMC9389857 36497616,https://doi.org/10.3390/ijerph192315544,Association between Internet Usage and Quality of Life of Elderly People in England: Evidence from the English Longitudinal Study of Ageing (ELSA).,"Vidiasratri AR, Bath PA, Bath PA.",,International journal of environmental research and public health,2022,2022-11-23,Y,Internet; Quality of life; Older People,,,"The WHO has stated that the number of senior citizens above age 65 across the world will double by the year 2050: in the UK, the whole population is projected to grow by about 2.5% over a decade, from mid-2018. Although people are living longer, they are not healthier in old age, and there is an increasing number of illnesses and disabilities in the ageing population, which have an impact on their overall well-being and quality of life (QoL). Alongside these trends, Internet technologies have improved and provide a wide range of information, including on medical and health issues. This study aimed to examine the association between the utilisation of the internet among older people in England and their QoL. This study utilised the English Longitudinal Study of Aging (ELSA), a longitudinal study of a representative sample of people aged 50 and over in England. The data from Wave 9 were analysed using bivariate analysis and logistic regression. The results show a strong association between QoL and utilisation of the Internet in older people, even when adjusting for demographic variables and health. Higher use of the internet was associated with older people being less likely to have higher QoL. The excessive use of the internet for communication and gathering information also contributed to lower QoL. From the findings, poorer QoL was also found in people in older age groups, in those who are married, and those who never suffer from chronic diseases. Our findings suggest that the quality of life in older people might not only be associated with the frequency of usage but also the purpose for which the internet is used; however, this relationship is complex and further research should explore this in greater depth. Further research should also investigate how older people's use of the Internet changed during the COVID-19 pandemic and the effects of this on the QoL in older age.",,doi:https://doi.org/10.3390/ijerph192315544; html:https://europepmc.org/articles/PMC9738189; pdf:https://europepmc.org/articles/PMC9738189?pdf=render 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render @@ -413,7 +413,7 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 33177070,https://doi.org/10.1136/bmj.m4262,"Accuracy of UK Rapid Test Consortium (UK-RTC) ""AbC-19 Rapid Test"" for detection of previous SARS-CoV-2 infection in key workers: test accuracy study.","Mulchandani R, Jones HE, Taylor-Phillips S, Shute J, Perry K, Jamarani S, Brooks T, Charlett A, Hickman M, Oliver I, Kaptoge S, Danesh J, Di Angelantonio E, Ades AE, Wyllie DH, EDSAB-HOME and COMPARE Investigators.",,BMJ (Clinical research ed.),2020,2020-11-11,Y,,,,"

Objective

To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Design

Test accuracy study.

Setting

Laboratory based evaluation.

Participants

2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors.

Main outcome measures

AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers.

Results

Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%).

Conclusions

AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to ""spectrum bias."" Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives.

Study registration

ISRCTN 56609224.",,doi:https://doi.org/10.1136/bmj.m4262; html:https://europepmc.org/articles/PMC7656121; pdf:https://europepmc.org/articles/PMC7656121?pdf=render 34644365,https://doi.org/10.1371/journal.pone.0258484,Cohort profile: The UK COVID-19 Public Experiences (COPE) prospective longitudinal mixed-methods study of health and well-being during the SARSCoV2 coronavirus pandemic.,"Phillips R, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Peddle S, Campbell S, Hughes K, Gillespie D, Sellars P, Pell B, Ashfield-Watt P, Akbari A, Seage CH, Perham N, Joseph-Williams N, Harrop E, Blaxland J, Wood F, Poortinga W, Wahl-Jorgensen K, James DH, Crone D, Thomas-Jones E, Hallingberg B.",,PloS one,2021,2021-10-13,Y,,,,"Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.",,doi:https://doi.org/10.1371/journal.pone.0258484; html:https://europepmc.org/articles/PMC8513913; pdf:https://europepmc.org/articles/PMC8513913?pdf=render 33743846,https://doi.org/10.1016/s1473-3099(21)00079-7,The potential health and economic value of SARS-CoV-2 vaccination alongside physical distancing in the UK: a transmission model-based future scenario analysis and economic evaluation.,"Sandmann FG, Davies NG, Vassall A, Edmunds WJ, Jit M, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Infectious diseases,2021,2021-03-18,Y,,,,"

Background

In response to the COVID-19 pandemic, the UK first adopted physical distancing measures in March, 2020. Vaccines against SARS-CoV-2 became available in December, 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing in the UK to gain insights about possible future scenarios in a post-vaccination era.

Methods

We used an age-structured dynamic transmission and economic model to explore different scenarios of UK mass immunisation programmes over 10 years. We compared vaccinating 75% of individuals aged 15 years or older (and annually revaccinating 50% of individuals aged 15-64 years and 75% of individuals aged 65 years or older) to no vaccination. We assumed either 50% vaccine efficacy against disease and 45-week protection (worst-case scenario) or 95% vaccine efficacy against infection and 3-year protection (best-case scenario). Natural immunity was assumed to wane within 45 weeks. We also explored the additional impact of physical distancing on vaccination by assuming either an initial lockdown followed by voluntary physical distancing, or an initial lockdown followed by increased physical distancing mandated above a certain threshold of incident daily infections. We considered benefits in terms of quality-adjusted life-years (QALYs) and costs, both to the health-care payer and the national economy. We discounted future costs and QALYs at 3·5% annually and assumed a monetary value per QALY of £20 000 and a conservative long-run cost per vaccine dose of £15. We explored and varied these parameters in sensitivity analyses. We expressed the health and economic benefits of each scenario with the net monetary value: QALYs × (monetary value per QALY) - costs.

Findings

Without the initial lockdown, vaccination, and increased physical distancing, we estimated 148·0 million (95% uncertainty interval 48·5-198·8) COVID-19 cases and 3·1 million (0·84-4·5) deaths would occur in the UK over 10 years. In the best-case scenario, vaccination minimises community transmission without future periods of increased physical distancing, whereas SARS-CoV-2 becomes endemic with biannual epidemics in the worst-case scenario. Ongoing transmission is also expected in intermediate scenarios with vaccine efficacy similar to published clinical trial data. From a health-care perspective, introducing vaccination leads to incremental net monetary values ranging from £12·0 billion to £334·7 billion in the best-case scenario and from -£1·1 billion to £56·9 billion in the worst-case scenario. Incremental net monetary values of increased physical distancing might be negative from a societal perspective if national economy losses are persistent and large.

Interpretation

Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Smaller outbreaks could continue even with vaccines, but population-wide implementation of increased physical distancing might no longer be justifiable. Our study provides early insights about possible future post-vaccination scenarios from an economic and epidemiological perspective.

Funding

National Institute for Health Research, European Commission, Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S1473-3099(21)00079-7; html:https://europepmc.org/articles/PMC7972313; doi:https://doi.org/10.1016/s1473-3099(21)00079-7 -35247983,https://doi.org/10.1186/s12877-021-02673-1,"Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.","Henkens MTHM, Raafs AG, Verdonschot JAJ, Linschoten M, van Smeden M, Wang P, van der Hooft BHM, Tieleman R, Janssen MLF, Ter Bekke RMA, Hazebroek MR, van der Horst ICC, Asselbergs FW, Magdelijns FJH, Heymans SRB, CAPACITY-COVID collaborative consortium.",,BMC geriatrics,2022,2022-03-05,Y,Mortality; Hospitalization; Netherlands; Mediation Analysis; Covid-19,,,"

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).",,doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render +35247983,https://doi.org/10.1186/s12877-021-02673-1,"Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.","Henkens MTHM, Raafs AG, Verdonschot JAJ, Linschoten M, van Smeden M, Wang P, van der Hooft BHM, Tieleman R, Janssen MLF, Ter Bekke RMA, Hazebroek MR, van der Horst ICC, Asselbergs FW, Magdelijns FJH, Heymans SRB, CAPACITY-COVID collaborative consortium.",,BMC geriatrics,2022,2022-03-05,Y,Mortality; Hospitalization; Netherlands; Mediation Analysis; Covid-19,,,"

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).",,doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render; doi:https://doi.org/10.1186/s12877-021-02673-1 33087179,https://doi.org/10.1186/s12916-020-01790-9,Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.,"Russell TW, Golding N, Hellewell J, Abbott S, Wright L, Pearson CAB, van Zandvoort K, Jarvis CI, Gibbs H, Liu Y, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,BMC medicine,2020,2020-10-22,Y,Surveillance; Situational Awareness; Under-reporting; Case Ascertainment; Outbreak Analysis; Covid-19; Sars-cov-2,,,"

Background

Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.

Methods

Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.

Results

Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6-24%) (Belgium).

Conclusions

We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.",,doi:https://doi.org/10.1186/s12916-020-01790-9; html:https://europepmc.org/articles/PMC7577796; pdf:https://europepmc.org/articles/PMC7577796?pdf=render 37561116,https://doi.org/10.7554/elife.85332,Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP.,"Lemanska A, Andrews C, Fisher L, Bacon S, Frampton AE, Mehrkar A, Inglesby P, Davy S, Roberts K, Patalay P, Goldacre B, MacKenna B, OpenSAFELY Collaborative, Walker AJ.",,eLife,2023,2023-08-10,Y,Human; Pancreatic cancer; epidemiology; Global Health; Healthcare; Healthcare Crisis; Covid-19; Healthcare Disruption,,,"

Background

Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic.

Methods

With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates.

Results

The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (±11 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital admissions, and deaths were not affected.

Conclusions

The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.

Funding

This work was jointly funded by the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). This work was funded by Medical Research Council (MRC) grant reference MR/W021390/1 as part of the postdoctoral fellowship awarded to AL and undertaken at the Bennett Institute, University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UKHSA), or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.",,doi:https://doi.org/10.7554/eLife.85332; html:https://europepmc.org/articles/PMC10414967; pdf:https://europepmc.org/articles/PMC10414967?pdf=render 32576605,https://doi.org/10.1136/jech-2020-214051,Efficacy of contact tracing for the containment of the 2019 novel coronavirus (COVID-19).,"Keeling MJ, Hollingsworth TD, Read JM.",,Journal of epidemiology and community health,2020,2020-06-23,Y,epidemiology; Communicable Diseases; Public Health Policy; Disease Modeling,,,"

Objective

Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel coronavirus (COVID-19) from China and elsewhere into the UK highlights the need to understand the impact of contact tracing as a control measure.

Design

Detailed survey information on social encounters from over 5800 respondents is coupled to predictive models of contact tracing and control. This is used to investigate the likely efficacy of contact tracing and the distribution of secondary cases that may go untraced.

Results

Taking recent estimates for COVID-19 transmission we predict that under effective contact tracing less than 1 in 6 cases will generate any subsequent untraced infections, although this comes at a high logistical burden with an average of 36 individuals traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we find that tracing using a contact definition requiring more than 4 hours of contact is unlikely to control spread.

Conclusions

The current contact tracing strategy within the UK is likely to identify a sufficient proportion of infected individuals such that subsequent spread could be prevented, although the ultimate success will depend on the rapid detection of cases and isolation of contacts. Given the burden of tracing a large number of contacts to find new cases, there is the potential the system could be overwhelmed if imports of infection occur at a rapid rate.",,doi:https://doi.org/10.1136/jech-2020-214051; html:https://europepmc.org/articles/PMC7307459; pdf:https://europepmc.org/articles/PMC7307459?pdf=render; pdf:https://jech.bmj.com/content/jech/74/10/861.full.pdf @@ -421,12 +421,13 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 36749628,https://doi.org/10.2196/42449,Charting a Course for Smartphones and Wearables to Transform Population Health Research.,"Dixon WG, van der Veer SN, Ali SM, Laidlaw L, Dobson RJB, Sudlow C, Chico T, MacArthur JAL, Doherty A.",,Journal of medical Internet research,2023,2023-02-07,Y,Research; Health; Clinical; Data; Digital; Devices; Wearable; Mhealth; Mobile Health; Person-generated Health Data; Population Health Research,,,"The use of data from smartphones and wearable devices has huge potential for population health research, given the high level of device ownership; the range of novel health-relevant data types available from consumer devices; and the frequency and duration with which data are, or could be, collected. Yet, the uptake and success of large-scale mobile health research in the last decade have not met this intensely promoted opportunity. We make the argument that digital person-generated health data are required and necessary to answer many top priority research questions, using illustrative examples taken from the James Lind Alliance Priority Setting Partnerships. We then summarize the findings from 2 UK initiatives that considered the challenges and possible solutions for what needs to be done and how such solutions can be implemented to realize the future opportunities of digital person-generated health data for clinically important population health research. Examples of important areas that must be addressed to advance the field include digital inequality and possible selection bias; easy access for researchers to the appropriate data collection tools, including how best to harmonize data items; analysis methodologies for time series data; patient and public involvement and engagement methods for optimizing recruitment, retention, and public trust; and methods for providing research participants with greater control over their data. There is also a major opportunity, provided through the linkage of digital person-generated health data to routinely collected data, to support novel population health research, bringing together clinician-reported and patient-reported measures. We recognize that well-conducted studies need a wide range of diverse challenges to be skillfully addressed in unison (eg, challenges regarding epidemiology, data science and biostatistics, psychometrics, behavioral and social science, software engineering, user interface design, information governance, data management, and patient and public involvement and engagement). Consequently, progress would be accelerated by the establishment of a new interdisciplinary community where all relevant and necessary skills are brought together to allow for excellence throughout the life cycle of a research study. This will require a partnership of diverse people, methods, and technologies. If done right, the synergy of such a partnership has the potential to transform many millions of people's lives for the better.",,doi:https://doi.org/10.2196/42449; html:https://europepmc.org/articles/PMC7614184; pdf:https://europepmc.org/articles/PMC7614184?pdf=render 34310590,https://doi.org/10.1371/journal.pcbi.1009098,Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era.,"Prem K, Zandvoort KV, Klepac P, Eggo RM, Davies NG, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Cook AR, Jit M.",,PLoS computational biology,2021,2021-07-26,Y,,,,"Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.",,doi:https://doi.org/10.1371/journal.pcbi.1009098; html:https://europepmc.org/articles/PMC8354454; pdf:https://europepmc.org/articles/PMC8354454?pdf=render 34161326,https://doi.org/10.1371/journal.pcbi.1009121,Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values.,"Cavallaro M, Moiz H, Keeling MJ, McCarthy ND.",,PLoS computational biology,2021,2021-06-23,Y,,,,"Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.",,doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render +34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render; pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3 37123891,https://doi.org/10.1016/j.heliyon.2023.e15143,Disclosure control of machine learning models from trusted research environments (TRE): New challenges and opportunities.,"Mansouri-Benssassi E, Rogers S, Reel S, Malone M, Smith J, Ritchie F, Jefferson E.",,Heliyon,2023,2023-04-03,Y,AI; Machine Learning; Data Privacy; Safe Haven; Disclosure Control; Trusted Research Environment,,,"

Introduction

Artificial intelligence (AI) applications in healthcare and medicine have increased in recent years. To enable access to personal data, Trusted Research Environments (TREs) (otherwise known as Safe Havens) provide safe and secure environments in which researchers can access sensitive personal data and develop AI (in particular machine learning (ML)) models. However, currently few TREs support the training of ML models in part due to a gap in the practical decision-making guidance for TREs in handling model disclosure. Specifically, the training of ML models creates a need to disclose new types of outputs from TREs. Although TREs have clear policies for the disclosure of statistical outputs, the extent to which trained models can leak personal training data once released is not well understood.

Background

We review, for a general audience, different types of ML models and their applicability within healthcare. We explain the outputs from training a ML model and how trained ML models can be vulnerable to external attacks to discover personal data encoded within the model.

Risks

We present the challenges for disclosure control of trained ML models in the context of training and exporting models from TREs. We provide insights and analyse methods that could be introduced within TREs to mitigate the risk of privacy breaches when disclosing trained models.

Discussion

Although specific guidelines and policies exist for statistical disclosure controls in TREs, they do not satisfactorily address these new types of output requests; i.e., trained ML models. There is significant potential for new interdisciplinary research opportunities in developing and adapting policies and tools for safely disclosing ML outputs from TREs.",,doi:https://doi.org/10.1016/j.heliyon.2023.e15143; html:https://europepmc.org/articles/PMC10130764; pdf:https://europepmc.org/articles/PMC10130764?pdf=render 32400358,https://doi.org/10.2807/1560-7917.es.2020.25.18.2000632,"Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020.","Jit M, Jombart T, Nightingale ES, Endo A, Abbott S, LSHTM Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Edmunds WJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-05-01,Y,Surveillance; intensive care unit; mathematical model; Reproduction Number; Sars-cov-2; Coronavirus Disease 2019,,,"An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000-173,000) new cases and 258 (95% CrI: 220-319) new critical care reports, with 527,000 (95% CrI: 362,000-797,000) cumulative cases since 16 February.","The authors of this paper estimate the number of cases and spread of COVID-19 using data on critical care admissions within the UK, from a period of February to March 2020. Their results suggest that the UK had hundreds of thousands of COVID-19 cases by the time the national lockdown was implemented. They highlight the usefulness of surveilling critical care data to better understand the dynamics of the epidemic and better inform the response measures.",doi:https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000632; html:https://europepmc.org/articles/PMC7219029; pdf:https://europepmc.org/articles/PMC7219029?pdf=render 35025917,https://doi.org/10.1371/journal.pone.0261142,Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.,"Bechman K, Yates M, Mann K, Nagra D, Smith LJ, Rutherford AI, Patel A, Periselneris J, Walder D, Dobson RJB, Kraljevic Z, Teo JHT, Bernal W, Barker R, Galloway JB, Norton S.",,PloS one,2022,2022-01-13,Y,,,,"

Background

The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves.

Methods

The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.

Results

There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87].

Conclusion

There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.",,doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable 36658423,https://doi.org/10.1038/s41591-022-02158-7,The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.,"Dale CE, Takhar R, Carragher R, Katsoulis M, Torabi F, Duffield S, Kent S, Mueller T, Kurdi A, Le Anh TN, McTaggart S, Abbasizanjani H, Hollings S, Scourfield A, Lyons RA, Griffiths R, Lyons J, Davies G, Harris D, Handy A, Mizani MA, Tomlinson C, Thygesen JH, Ashworth M, Denaxas S, Banerjee A, Sterne JAC, Brown P, Bullard I, Priedon R, Mamas MA, Slee A, Lorgelly P, Pirmohamed M, Khunti K, Morris AD, Sudlow C, Akbari A, Bennie M, Sattar N, Sofat R, CVD-COVID-UK Consortium.",,Nature medicine,2023,2023-01-19,N,,,,"How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.",,doi:https://doi.org/10.1038/s41591-022-02158-7; pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf -37561812,https://doi.org/10.1371/journal.pcbi.1011368,Call detail record aggregation methodology impacts infectious disease models informed by human mobility.,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,PLoS computational biology,2023,2023-08-10,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, ""all pairs,"" is designed to retain long distance network connections while the other, ""sequential"" methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and the transmissibility of infections. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.",,doi:https://doi.org/10.1371/journal.pcbi.1011368; html:https://europepmc.org/articles/PMC10443843; pdf:https://europepmc.org/articles/PMC10443843?pdf=render 33821553,https://doi.org/10.1002/jia2.25697,The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.,"Booton RD, Fu G, MacGregor L, Li J, Ong JJ, Tucker JD, Turner KM, Tang W, Vickerman P, Mitchell KM.",,Journal of the International AIDS Society,2021,2021-04-01,Y,Modelling; Hiv Transmission; Men Who Have Sex With Men; People’s Republic Of China; Key And Vulnerable Populations; Covid-19 Pandemic,,,"

Introduction

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

Methods

Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020.

Results

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

Conclusions

The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.",,doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render +37561812,https://doi.org/10.1371/journal.pcbi.1011368,Call detail record aggregation methodology impacts infectious disease models informed by human mobility.,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,PLoS computational biology,2023,2023-08-10,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, ""all pairs,"" is designed to retain long distance network connections while the other, ""sequential"" methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and the transmissibility of infections. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.",,doi:https://doi.org/10.1371/journal.pcbi.1011368; html:https://europepmc.org/articles/PMC10443843; pdf:https://europepmc.org/articles/PMC10443843?pdf=render 34139154,https://doi.org/10.1016/j.cels.2021.05.005,A time-resolved proteomic and prognostic map of COVID-19.,"Demichev V, Tober-Lau P, Lemke O, Nazarenko T, Thibeault C, Whitwell H, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Aulakh SK, Helbig ET, Stubbemann P, Lippert LJ, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Ralser M, Kurth F.",,Cell systems,2021,2021-06-14,Y,Proteomics; Biomarkers; Physiological parameters; Machine Learning; Disease Prognosis; Clinical Disease Progression; Patient Trajectories; Longitudinal Profiling; Covid-19,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.",,doi:https://doi.org/10.1016/j.cels.2021.05.005; html:https://europepmc.org/articles/PMC8201874; doi:https://doi.org/10.1016/j.cels.2021.05.005 36845321,https://doi.org/10.12688/wellcomeopenres.17403.2,"Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.","Moreno-Martos D, Verhamme K, Ostropolets A, Kostka K, Duarte-Sales T, Prieto-Alhambra D, Alshammari TM, Alghoul H, Ahmed WU, Blacketer C, DuVall S, Lai L, Matheny M, Nyberg F, Posada J, Rijnbeek P, Spotnitz M, Sena A, Shah N, Suchard M, Chan You S, Hripcsak G, Ryan P, Morales D.",,Wellcome open research,2022,2022-03-24,Y,COPD; Coronavirus; Epidemiology.; Sars-cov-2; Covid,,,"Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.",,doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render 34252085,https://doi.org/10.1371/journal.pcbi.1009162,Detecting behavioural changes in human movement to inform the spatial scale of interventions against COVID-19.,"Gibbs H, Nightingale E, Liu Y, Cheshire J, Danon L, Smeeth L, Pearson CAB, Grundy C, LSHTM CMMID COVID-19 working group, Kucharski AJ, Eggo RM.",,PLoS computational biology,2021,2021-07-12,Y,,,,"On March 23 2020, the UK enacted an intensive, nationwide lockdown to mitigate transmission of COVID-19. As restrictions began to ease, more localized interventions were used to target resurgences in transmission. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to targeting interventions at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence. We use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time. We found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance connections central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas. We propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions.",,doi:https://doi.org/10.1371/journal.pcbi.1009162; html:https://europepmc.org/articles/PMC8297940; pdf:https://europepmc.org/articles/PMC8297940?pdf=render @@ -455,8 +456,8 @@ PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in W 36649943,https://doi.org/10.1136/bmjoq-2021-001704,Benefits of electronic charts in intensive care and during a world health pandemic: advantages of the technology age.,"Pankhurst T, Lucas L, Ryan S, Ragdale C, Gyves H, Denner L, Young I, Rathbone L, Shah A, McKee D, Coleman JJ, Evison F, Atia J, Rosser D, Garrick M, Baker R, Gallier S, Ball S.",,BMJ open quality,2023,2023-01-01,Y,Evaluation Methodology; Critical Care; Electronic Health Records,,,"

Aims and objectives

This study sets out to describe benefits from the implementation of electronic observation charting in intensive care units (ICU). This was an extension to the existing hospital wide digital health system. We evaluated error reduction, time-savings and the costs associated with conversion from paper to digital records. The world health emergency of COVID-19 placed extraordinary strain on ICU and staff opinion was evaluated to test how well the electronic system performed.

Methods

A clinically led project group working directly with programmers developed an electronic patient record for intensive care. Data error rates, time to add data and to make calculations were studied before and after the introduction of electronic charts. User feedback was sought pre and post go-live (during the COVID-19 pandemic) and financial implications were calculated by the hospital finance teams.

Results

Error rates equating to 219 000/year were avoided by conversion to electronic charts. Time saved was the equivalent of a nursing shift each day. Recurrent cost savings per year were estimated to be £257k. Staff were overwhelmingly positive about electronic charts in ICU, even during a health pandemic and despite redeployment into intensive care where they were using the electronic charts for the first time.

Discussion

Electronic ICU charts have been successfully introduced into our institution with benefits in terms of patient safety through error reduction and improved care through release of nursing time. Costs have been reduced. Staff feel supported by the digital system and report it to be helpful even during redeployment and in the unfamiliar environment of intensive care.",,doi:https://doi.org/10.1136/bmjoq-2021-001704; html:https://europepmc.org/articles/PMC9853220; pdf:https://europepmc.org/articles/PMC9853220?pdf=render 33704068,https://doi.org/10.7554/elife.64827,Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.,"Gisby J, Clarke CL, Medjeral-Thomas N, Malik TH, Papadaki A, Mortimer PM, Buang NB, Lewis S, Pereira M, Toulza F, Fagnano E, Mawhin MA, Dutton EE, Tapeng L, Richard AC, Kirk PD, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M, Thomas DC, Peters JE.",,eLife,2021,2021-03-11,Y,Human; Cytokines; Proteomics; Inflammation; Medicine; Biomarkers; immunology; Longitudinal; End-stage Kidney Disease; Covid-19,,,"End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.",,doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render 33024096,https://doi.org/10.1038/s41467-020-18783-0,Changing travel patterns in China during the early stages of the COVID-19 pandemic.,"Gibbs H, Liu Y, Pearson CAB, Jarvis CI, Grundy C, Quilty BJ, Diamond C, LSHTM CMMID COVID-19 working group, Eggo RM.",,Nature communications,2020,2020-10-06,Y,,,,"Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigate the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020, and discuss their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower healthcare capacity. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and did not lead to structural reorganisation of the transportation network during the study period.",,doi:https://doi.org/10.1038/s41467-020-18783-0; html:https://europepmc.org/articles/PMC7538915; pdf:https://europepmc.org/articles/PMC7538915?pdf=render -36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render 34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render +36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render 32907855,https://doi.org/10.1136/bmj.m3339,Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.,"Knight SR, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Gupta R, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Noursadeghi M, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle LC, Openshaw PJ, Baillie JK, Semple MG, Docherty AB, Harrison EM, ISARIC4C investigators.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"

Objective

To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).

Design

Prospective observational cohort study.

Setting

International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.

Main outcome measure

In-hospital mortality.

Results

35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).

Conclusions

An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.

Study registration

ISRCTN66726260.",,doi:https://doi.org/10.1136/bmj.m3339; html:https://europepmc.org/articles/PMC7116472; pdf:https://europepmc.org/articles/PMC7116472?pdf=render 35991675,https://doi.org/10.1016/j.lana.2022.100335,Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.,"Bastos LSL, Aguilar S, Rache B, Maçaira P, Baião F, Cerbino-Neto J, Rocha R, Hamacher S, Ranzani OT, Bozza FA.",,Lancet regional health. Americas,2022,2022-08-17,Y,Vaccine; Socioeconomic Factors; Human Development; Primary Healthcare; Low-and-middle-income Countries; Covid19,,,"

Background

There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage.

Methods

We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels.

Findings

From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations.

Interpretation

In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations.

Funding

This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.",,doi:https://doi.org/10.1016/j.lana.2022.100335; html:https://europepmc.org/articles/PMC9381845; pdf:https://europepmc.org/articles/PMC9381845?pdf=render 33661754,https://doi.org/10.2196/21547,Implementation of the COVID-19 Vulnerability Index Across an International Network of Health Care Data Sets: Collaborative External Validation Study.,"Reps JM, Kim C, Williams RD, Markus AF, Yang C, Duarte-Salles T, Falconer T, Jonnagaddala J, Williams A, Fernández-Bertolín S, DuVall SL, Kostka K, Rao G, Shoaibi A, Ostropolets A, Spotnitz ME, Zhang L, Casajust P, Steyerberg EW, Nyberg F, Kaas-Hansen BS, Choi YH, Morales D, Liaw ST, Abrahão MTF, Areia C, Matheny ME, Lynch KE, Aragón M, Park RW, Hripcsak G, Reich CG, Suchard MA, You SC, Ryan PB, Prieto-Alhambra D, Rijnbeek PR.",,JMIR medical informatics,2021,2021-04-05,Y,Prediction; Modeling; Observation; decision-making; Bias; Hospitalization; risk; Transportability; Prognostic Model; Datasets; External Validation; Covid-19; C-19,,,"

Background

SARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the ""prediction model risk of bias assessment"" criteria, and it has not been externally validated.

Objective

The aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases.

Methods

We followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia.

Results

The internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68.

Conclusions

Our results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.",,doi:https://doi.org/10.2196/21547; html:https://europepmc.org/articles/PMC8023380 @@ -470,8 +471,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 34098341,https://doi.org/10.1016/j.ebiom.2021.103414,Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study.,"Jones HE, Mulchandani R, Taylor-Phillips S, Ades AE, Shute J, Perry KR, Chandra NL, Brooks T, Charlett A, Hickman M, Oliver I, Kaptoge S, Danesh J, Di Angelantonio E, Wyllie D, COMPARE study investigators, EDSAB-HOME investigators.",,EBioMedicine,2021,2021-06-04,Y,Seroepidemiology; Rapid Testing; Serosurveillance; Lateral Flow Devices; Covid-19,,,"

Background

SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy.

Methods

In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices.

Findings

We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19TM device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations (""spectrum effects""), but the extent of this varied by device.

Interpretation

The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives.

Funding

Public Health England.",,doi:https://doi.org/10.1016/j.ebiom.2021.103414; html:https://europepmc.org/articles/PMC8176919; pdf:https://europepmc.org/articles/PMC8176919?pdf=render 33319712,https://doi.org/10.1186/s12911-020-01336-2,Towards semantic interoperability: finding and repairing hidden contradictions in biomedical ontologies.,"Slater LT, Gkoutos GV, Hoehndorf R.",,BMC medical informatics and decision making,2020,2020-12-15,Y,Automated Reasoning; Ontology Interoperability,,,"

Background

Ontologies are widely used throughout the biomedical domain. These ontologies formally represent the classes and relations assumed to exist within a domain. As scientific domains are deeply interlinked, so too are their representations. While individual ontologies can be tested for consistency and coherency using automated reasoning methods, systematically combining ontologies of multiple domains together may reveal previously hidden contradictions.

Methods

We developed a method that tests for hidden unsatisfiabilities in an ontology that arise when combined with other ontologies. For this purpose, we combined sets of ontologies and use automated reasoning to determine whether unsatisfiable classes are present. In addition, we designed and implemented a novel algorithm that can determine justifications for contradictions across extremely large and complicated ontologies, and use these justifications to semi-automatically repair ontologies by identifying a small set of axioms that, when removed, result in a consistent and coherent set of ontologies.

Results

We tested the mutual consistency of the OBO Foundry and the OBO ontologies and find that the combined OBO Foundry gives rise to at least 636 unsatisfiable classes, while the OBO ontologies give rise to more than 300,000 unsatisfiable classes. We also applied our semi-automatic repair algorithm to each combination of OBO ontologies that resulted in unsatisfiable classes, finding that only 117 axioms could be removed to account for all cases of unsatisfiability across all OBO ontologies.

Conclusions

We identified a large set of hidden unsatisfiability across a broad range of biomedical ontologies, and we find that this large set of unsatisfiable classes is the result of a relatively small amount of axiomatic disagreements. Our results show that hidden unsatisfiability is a serious problem in ontology interoperability; however, our results also provide a way towards more consistent ontologies by addressing the issues we identified.",,doi:https://doi.org/10.1186/s12911-020-01336-2; html:https://europepmc.org/articles/PMC7736131; pdf:https://europepmc.org/articles/PMC7736131?pdf=render 32401709,https://doi.org/10.1016/s2468-2667(20)30112-2,COVID-19: a public health approach to manage domestic violence is needed.,"Chandan JS, Taylor J, Bradbury-Jones C, Nirantharakumar K, Kane E, Bandyopadhyay S.",,The Lancet. Public health,2020,2020-05-10,Y,,,,,Chandan et al. comment on the effect the covid pandemic may have on domestic violence and propose surveillance for domestic violence is needed. ,doi:https://doi.org/10.1016/S2468-2667(20)30112-2; html:https://europepmc.org/articles/PMC7252171; pdf:https://europepmc.org/articles/PMC7252171?pdf=render -36949447,https://doi.org/10.1186/s12889-023-15345-z,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic.,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,BMC public health,2023,2023-03-22,Y,Colorectal Cancer; Inequalities; Bowel; Ethnicity; Cancer Screening; Covid-19,,,"

Background

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

Methods

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

Results

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

Conclusion

Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.",,doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render 33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Swab Test; Covid-19,,,"Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render +36949447,https://doi.org/10.1186/s12889-023-15345-z,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic.,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,BMC public health,2023,2023-03-22,Y,Colorectal Cancer; Inequalities; Bowel; Ethnicity; Cancer Screening; Covid-19,,,"

Background

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

Methods

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

Results

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

Conclusion

Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.",,doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render 33612430,https://doi.org/10.1016/s2589-7500(21)00017-0,Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.,"Mansfield KE, Mathur R, Tazare J, Henderson AD, Mulick AR, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Cook S, Wong AYS, Strongman H, Wing K, Warren-Gash C, Cadogan SL, Smeeth L, Hayes JF, Quint JK, McKee M, Langan SM.",,The Lancet. Digital health,2021,2021-02-18,Y,,,,"

Background

There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic.

Methods

Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28).

Findings

The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels.

Interpretation

There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision.

Funding

Wellcome Trust Senior Fellowship, Health Data Research UK.",,doi:https://doi.org/10.1016/S2589-7500(21)00017-0; html:https://europepmc.org/articles/PMC7985613; pdf:https://europepmc.org/articles/PMC7985613?pdf=render 36280346,https://doi.org/10.1136/heartjnl-2022-321492,Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.,"Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2022,2022-12-22,Y,epidemiology; Covid-19,,,"

Objective

To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.",,doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render 36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"

Objectives

To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.

Design

Retrospective assessment of routinely collected data from electronic healthcare records.

Setting

Single large urban tertiary care centre.

Participants

All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.

Main outcome measures

Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.

Results

7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.

Conclusions

The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render @@ -485,9 +486,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 35210898,https://doi.org/10.2147/por.s353400,Deriving a Standardised Recommended Respiratory Disease Codelist Repository for Future Research.,"MacRae C, Whittaker H, Mukherjee M, Daines L, Morgan A, Iwundu C, Alsallakh M, Vasileiou E, O'Rourke E, Williams AT, Stone PW, Sheikh A, Quint JK.",,Pragmatic and observational research,2022,2022-02-16,Y,Asthma; COPD; Respiratory Tract Infections; Electronic Healthcare Records,,,"

Background

Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes.

Methods

We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided in article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature.

Results

Medline searches returned 1126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions.

Conclusion

Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made, greater consistency and transparency across studies using routine data to study respiratory diseases are needed.",,doi:https://doi.org/10.2147/POR.S353400; html:https://europepmc.org/articles/PMC8859726; pdf:https://europepmc.org/articles/PMC8859726?pdf=render 34661663,https://doi.org/10.1001/jamanetworkopen.2021.29639,Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.,"Izadi Z, Brenner EJ, Mahil SK, Dand N, Yiu ZZN, Yates M, Ungaro RC, Zhang X, Agrawal M, Colombel JF, Gianfrancesco MA, Hyrich KL, Strangfeld A, Carmona L, Mateus EF, Lawson-Tovey S, Klingberg E, Cuomo G, Caprioli M, Cruz-Machado AR, Mazeda Pereira AC, Hasseli R, Pfeil A, Lorenz HM, Hoyer BF, Trupin L, Rush S, Katz P, Schmajuk G, Jacobsohn L, Seet AM, Al Emadi S, Wise L, Gilbert EL, Duarte-García A, Valenzuela-Almada MO, Isnardi CA, Quintana R, Soriano ER, Hsu TY, D'Silva KM, Sparks JA, Patel NJ, Xavier RM, Marques CDL, Kakehasi AM, Flipo RM, Claudepierre P, Cantagrel A, Goupille P, Wallace ZS, Bhana S, Costello W, Grainger R, Hausmann JS, Liew JW, Sirotich E, Sufka P, Robinson PC, Machado PM, Griffiths CEM, Barker JN, Smith CH, Yazdany J, Kappelman MD, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Allianc, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Alliance (GRA).",,JAMA network open,2021,2021-10-01,Y,,,,"

Importance

Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood.

Objective

To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs.

Design, setting, and participants

This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included.

Exposures

Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy.

Main outcomes and measures

The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations.

Results

A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone.

Conclusions and relevance

In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.",,doi:https://doi.org/10.1001/jamanetworkopen.2021.29639; html:https://europepmc.org/articles/PMC8524310 35260393,https://doi.org/10.1136/bmjgh-2021-008099,Overcoming disruptions in essential health services during the COVID-19 pandemic in Mexico. ,"Doubova SV, Robledo-Aburto ZA, Duque-Molina C, Borrayo-Sánchez G, González-León M, Avilés-Hernández R, Contreras-Sánchez SE, Leslie HH, Kruk M, Pérez-Cuevas R, Arsenault C.",,BMJ global health,2022,2022-03-01,Y,,,,,,doi:https://doi.org/10.1136/bmjgh-2021-008099; html:https://europepmc.org/articles/PMC8905410; pdf:https://europepmc.org/articles/PMC8905410?pdf=render -34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render -34740937,https://doi.org/10.1136/bmjopen-2021-056601,Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study.,"Patel R, Smeraldi F, Abdollahyan M, Irving J, Bessant C.",,BMJ open,2021,2021-11-05,Y,information technology; Health Informatics; Covid-19,,,"

Objectives

Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users.

Setting and design

We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19.

Primary outcome measures

(1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities.

Results

Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity.

Conclusions

We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.",,doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render 33414147,https://doi.org/10.1136/bmjopen-2020-041536,Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.,"Booton RD, MacGregor L, Vass L, Looker KJ, Hyams C, Bright PD, Harding I, Lazarus R, Hamilton F, Lawson D, Danon L, Pratt A, Wood R, Brooks-Pollock E, Turner KME.",,BMJ open,2021,2021-01-07,Y,Infection control; epidemiology; Public Health,,,"

Objectives

To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.

Design

Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.

Setting

SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.

Participants

Publicly available data on patients with COVID-19.

Primary and secondary outcome measures

The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.

Results

SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).

Conclusions

The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.",,doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render +34740937,https://doi.org/10.1136/bmjopen-2021-056601,Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study.,"Patel R, Smeraldi F, Abdollahyan M, Irving J, Bessant C.",,BMJ open,2021,2021-11-05,Y,information technology; Health Informatics; Covid-19,,,"

Objectives

Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users.

Setting and design

We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19.

Primary outcome measures

(1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities.

Results

Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity.

Conclusions

We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.",,doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render 35288697,https://doi.org/10.1038/s41591-022-01750-1,COVID-19 and resilience of healthcare systems in ten countries.,"Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar Á, Pérez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Guiñez F, Bauhoff S, Kruk ME.",,Nature medicine,2022,2022-03-14,Y,,,,"Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",,doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render 36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render 34859617,https://doi.org/10.1002/edm2.309,The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.,"Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.",,"Endocrinology, diabetes & metabolism",2022,2021-12-03,Y,Diabetes; Complications; Covid-19,,,"

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.",,doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render @@ -497,14 +497,14 @@ PMC10464868,https://doi.org/,An overview of synthetic administrative data for re 32979970,https://doi.org/10.1016/s0140-6736(20)31966-8,Models for mortality require tailoring in the context of the COVID-19 pandemic - Authors' reply.,"Banerjee A, Pasea L, Denaxas S, Williams B, Hemingway H.",,"Lancet (London, England)",2020,2020-09-01,Y,,,,,,doi:https://doi.org/10.1016/S0140-6736(20)31966-8; html:https://europepmc.org/articles/PMC7515579; pdf:https://europepmc.org/articles/PMC7515579?pdf=render 34378227,https://doi.org/10.1111/tri.14010,"Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.","McKay SC, Lembach H, Hann A, Okoth K, Anderton J, Nirantharakumar K, Magill L, Torlinska B, Armstrong M, Mascaro J, Inston N, Pinkney T, Ranasinghe A, Borrows R, Ferguson J, Isaac J, Calvert M, Perera MTPR, Hartog H.",,Transplant international : official journal of the European Society for Organ Transplantation,2021,2021-09-16,Y,Isolation; Transplant; Mental health; Health-related Quality Of Life; Shielding; Covid-19,,,"Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.",,doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?pdf=render 37269003,https://doi.org/10.1186/s13643-023-02261-x,Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.,"Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",,Systematic reviews,2023,2023-06-02,Y,Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19,,,"

Background

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.

Methods

Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.

Results

Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.

Discussion

Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.

Systematic review registration

PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render -37311637,https://doi.org/10.1136/bmjopen-2023-071973,Number and timing of primary cleft lip and palate repair surgeries in England: whole nation study of electronic health records before and during the COVID-19 pandemic.,"Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",,BMJ open,2023,2023-06-13,Y,epidemiology; Paediatric Surgery; Covid-19,,,"

Objective

To quantify differences in number and timing of first primary cleft lip and palate (CLP) repair procedures during the first year of the COVID-19 pandemic (1 April 2020 to 31 March 2021; 2020/2021) compared with the preceding year (1 April 2019 to 31 March 2020; 2019/2021).

Design

National observational study of administrative hospital data.

Setting

National Health Service hospitals in England.

Study population

Children <5 years undergoing primary repair for an orofacial cleft Population Consensus and Surveys Classification of Interventions and Procedures-fourth revisions (OPCS-4) codes F031, F291).

Main exposure

Procedure date (2020/2021 vs 2019/2020).

Main outcomes

Numbers and timing (age in months) of first primary CLP procedures.

Results

1716 CLP primary repair procedures were included in the analysis. In 2020/2021, 774 CLP procedures were carried out compared with 942 in 2019/2020, a reduction of 17.8% (95% CI 9.5% to 25.4%). The reduction varied over time in 2020/2021, with no surgeries at all during the first 2 months (April and May 2020). Compared with 2019/2020, first primary lip repair procedures performed in 2020/2021 were delayed by 1.6 months on average (95% CI 0.9 to 2.2 months). Delays in primary palate repairs were smaller on average but varied across the nine geographical regions.

Conclusion

There were significant reductions in the number and delays in timing of first primary CLP repair procedures in England during the first year of the pandemic, which may affect long-term outcomes.",,doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render 34722933,https://doi.org/10.12688/wellcomeopenres.16507.1,The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.,"Stock SJ, Zoega H, Brockway M, Mulholland RH, Miller JE, Been JV, Wood R, Abok II, Alshaikh B, Ayede AI, Bacchini F, Bhutta ZA, Brew BK, Brook J, Calvert C, Campbell-Yeo M, Chan D, Chirombo J, Connor KL, Daly M, Einarsdóttir K, Fantasia I, Franklin M, Fraser A, Håberg SE, Hui L, Huicho L, Magnus MC, Morris AD, Nagy-Bonnard L, Nassar N, Nyadanu SD, Iyabode Olabisi D, Palmer KR, Pedersen LH, Pereira G, Racine-Poon A, Ranger M, Rihs T, Saner C, Sheikh A, Swift EM, Tooke L, Urquia ML, Whitehead C, Yilgwan C, Rodriguez N, Burgner D, Azad MB, iPOP Study Team.",,Wellcome open research,2021,2021-02-02,Y,Stillbirth; Low Birth Weight; Preterm Birth; Global Trends; Perinatal Outcomes; Covid-19; Pandemic Lockdowns,,,"Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread ""natural experiment"" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.",,doi:https://doi.org/10.12688/wellcomeopenres.16507.1; html:https://europepmc.org/articles/PMC8524299; pdf:https://europepmc.org/articles/PMC8524299?pdf=render +37311637,https://doi.org/10.1136/bmjopen-2023-071973,Number and timing of primary cleft lip and palate repair surgeries in England: whole nation study of electronic health records before and during the COVID-19 pandemic.,"Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",,BMJ open,2023,2023-06-13,Y,epidemiology; Paediatric Surgery; Covid-19,,,"

Objective

To quantify differences in number and timing of first primary cleft lip and palate (CLP) repair procedures during the first year of the COVID-19 pandemic (1 April 2020 to 31 March 2021; 2020/2021) compared with the preceding year (1 April 2019 to 31 March 2020; 2019/2021).

Design

National observational study of administrative hospital data.

Setting

National Health Service hospitals in England.

Study population

Children <5 years undergoing primary repair for an orofacial cleft Population Consensus and Surveys Classification of Interventions and Procedures-fourth revisions (OPCS-4) codes F031, F291).

Main exposure

Procedure date (2020/2021 vs 2019/2020).

Main outcomes

Numbers and timing (age in months) of first primary CLP procedures.

Results

1716 CLP primary repair procedures were included in the analysis. In 2020/2021, 774 CLP procedures were carried out compared with 942 in 2019/2020, a reduction of 17.8% (95% CI 9.5% to 25.4%). The reduction varied over time in 2020/2021, with no surgeries at all during the first 2 months (April and May 2020). Compared with 2019/2020, first primary lip repair procedures performed in 2020/2021 were delayed by 1.6 months on average (95% CI 0.9 to 2.2 months). Delays in primary palate repairs were smaller on average but varied across the nine geographical regions.

Conclusion

There were significant reductions in the number and delays in timing of first primary CLP repair procedures in England during the first year of the pandemic, which may affect long-term outcomes.",,doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render 37006328,https://doi.org/10.1093/braincomms/fcad065,"Infections among individuals with multiple sclerosis, Alzheimer's disease and Parkinson's disease.","Hu Y, Hu K, Song H, Pawitan Y, Piehl F, Fang F.",,Brain communications,2023,2023-03-16,Y,Multiple sclerosis; Alzheimer’s disease; Infections; Parkinson’s Disease,,,"A link between neurodegenerative diseases and infections has been previously reported. However, it is not clear to what extent such link is caused by confounding factors or to what extent it is intimately connected with the underlying conditions. Further, studies on the impact of infections on mortality risk following neurodegenerative diseases are rare. We analysed two data sets with different characteristics: (i) a community-based cohort from the UK Biobank with 2023 patients with multiple sclerosis, 2200 patients with Alzheimer's disease, 3050 patients with Parkinson's disease diagnosed before 1 March 2020 and 5 controls per case who were randomly selected and individually matched to the case; (ii) a Swedish Twin Registry cohort with 230 patients with multiple sclerosis, 885 patients with Alzheimer's disease and 626 patients with Parkinson's disease diagnosed before 31 December 2016 and their disease-free co-twins. The relative risk of infections after a diagnosis of neurodegenerative disease was estimated using stratified Cox models, with adjustment for differences in baseline characteristics. Causal mediation analyses of survival outcomes based on Cox models were performed to assess the impact of infections on mortality. Compared with matched controls or unaffected co-twins, we observed an elevated infection risk after diagnosis of neurodegenerative diseases, with a fully adjusted hazard ratio (95% confidence interval) of 2.45 (2.24-2.69) for multiple sclerosis, 5.06 (4.58-5.59) for Alzheimer's disease and 3.72 (3.44-4.01) for Parkinson's disease in the UK Biobank cohort, and 1.78 (1.21-2.62) for multiple sclerosis, 1.50 (1.19-1.88) for Alzheimer's disease and 2.30 (1.79-2.95) for Parkinson's disease in the twin cohort. Similar risk increases were observed when we analysed infections during the 5 years before diagnosis of the respective disease. Occurrence of infections after diagnosis had, however, relatively little impact on mortality, as mediation of infections on mortality (95% confidence interval) was estimated as 31.89% (26.83-37.11%) for multiple sclerosis, 13.38% (11.49-15.29%) for Alzheimer's disease and 18.85% (16.95-20.97%) for Parkinson's disease in the UK Biobank cohort, whereas it was 6.56% (-3.59 to 16.88%) for multiple sclerosis, -2.21% (-0.21 to 4.65%) for Parkinson's disease and -3.89% (-7.27 to -0.51%) for Alzheimer's disease in the twin cohort. Individuals with studied neurodegenerative diseases display an increased risk of infections independently of genetic and familial environment factors. A similar magnitude of risk increase is present prior to confirmed diagnosis, which may indicate a modulating effect of the studied neurological conditions on immune defences.",,doi:https://doi.org/10.1093/braincomms/fcad065; html:https://europepmc.org/articles/PMC10053639; pdf:https://europepmc.org/articles/PMC10053639?pdf=render 33716109,https://doi.org/10.1016/j.jinf.2021.03.002,Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.,"Chaudhry Z, Shawe-Taylor M, Rampling T, Cutfield T, Bidwell G, Chan XHS, Last A, Williams B, Logan S, Marks M, Esmail H.",,The Journal of infection,2021,2021-03-11,Y,Dexamethasone; Corticosteroids; Hospital; Readmissions; Covid-19,,,"

Objective

Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.

Methods

We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.

Results

196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.

Conclusions

Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.",,doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render; doi:https://doi.org/10.12688/wellcomeopenres.15786.1 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"

Background

Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.

Methods and findings

We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.

Conclusions and relevance

Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render 35677101,https://doi.org/10.23889/ijpds.v5i4.1715,"Impact of COVID-19 pandemic on community medication dispensing: a national cohort analysis in Wales, UK.","Torabi F, Akbari A, Bedston S, Davies G, Abbasizanjani H, Gravenor M, Griffiths R, Harris D, Jenkins N, Lyons J, Morris A, North L, Halcox J, Lyons RA.",,International journal of population data science,2020,2020-01-01,Y,Public Health; Covid-19; Dispensed Medication; Community Dispensing; Interactive Dispensing Dashboard,,,"

Background

Population-level information on dispensed medication provides insight on the distribution of treated morbidities, particularly if linked to other population-scale data at an individual-level.

Objective

To evaluate the impact of COVID-19 on dispensing patterns of medications.

Methods

Retrospective observational study using population-scale, individual-level dispensing records in Wales, UK. Total dispensed drug items for the population between 1 st January 2016 and 31 st December 2019 (3-years, pre-COVID-19) were compared to 2020 with follow up until 27 th July 2021 (COVID-19 period). We compared trends across all years and British National Formulary (BNF) chapters and highlighted the trends in three major chapters for 2019-21: 1-Cardiovascular system (CVD); 2-Central Nervous System (CNS); 3-Immunological & Vaccine. We developed an interactive dashboard to enable monitoring of changes as the pandemic evolves.

Result

Amongst all BNF chapters, 73,410,543 items were dispensed in 2020 compared to 74,121,180 items in 2019 demonstrating -0.96% relative decrease in 2020. Comparison of monthly patterns showed average difference (D) of -59,220 and average Relative Change (RC) of -0.74% between the number of dispensed items in 2020 and 2019. Maximum RC was observed in March 2020 (D = +1,224,909 and RC = +20.62), followed by second peak in June 2020 (D = +257,920, RC = +4.50%). A third peak was observed in September 2020 (D = +264,138, RC = +4.35%). Large increases in March 2020 were observed for CVD and CNS medications across all age groups. The Immunological and Vaccine products dropped to very low levels across all age groups and all months (including the March dispensing peak).

Conclusions

Reconfiguration of routine clinical services during COVID-19 led to substantial changes in community pharmacy drug dispensing. This change may contribute to a long-term burden of COVID-19, raising the importance of a comprehensive and timely monitoring of changes for evaluation of the potential impact on clinical care and outcomes.",,doi:https://doi.org/10.23889/ijpds.v5i4.1715; html:https://europepmc.org/articles/PMC9135049; pdf:https://europepmc.org/articles/PMC9135049?pdf=render -37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render +37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable 36802769,https://doi.org/10.1259/bjr.20201465,Applying machine learning classifiers to automate quality assessment of paediatric dynamic susceptibility contrast (DSC-) MRI data.,"Powell SJ, Withey SB, Sun Y, Grist JT, Novak J, MacPherson L, Abernethy L, Pizer B, Grundy R, Morgan PS, Jaspan T, Bailey S, Mitra D, Auer DP, Avula S, Arvanitis TN, Peet A.",,The British journal of radiology,2023,2023-02-20,Y,,,,"

Objective

Investigate the performance of qualitative review (QR) for assessing dynamic susceptibility contrast (DSC-) MRI data quality in paediatric normal brain and develop an automated alternative to QR.

Methods

1027 signal-time courses were assessed by Reviewer 1 using QR. 243 were additionally assessed by Reviewer 2 and % disagreements and Cohen's κ (κ) were calculated. The signal drop-to-noise ratio (SDNR), root mean square error (RMSE), full width half maximum (FWHM) and percentage signal recovery (PSR) were calculated for the 1027 signal-time courses. Data quality thresholds for each measure were determined using QR results. The measures and QR results trained machine learning classifiers. Sensitivity, specificity, precision, classification error and area under the curve from a receiver operating characteristic curve were calculated for each threshold and classifier.

Results

Comparing reviewers gave 7% disagreements and κ = 0.83. Data quality thresholds of: 7.6 for SDNR; 0.019 for RMSE; 3 s and 19 s for FWHM; and 42.9 and 130.4% for PSR were produced. SDNR gave the best sensitivity, specificity, precision, classification error and area under the curve values of 0.86, 0.86, 0.93, 14.2% and 0.83. Random forest was the best machine learning classifier, giving sensitivity, specificity, precision, classification error and area under the curve of 0.94, 0.83, 0.93, 9.3% and 0.89.

Conclusion

The reviewers showed good agreement. Machine learning classifiers trained on signal-time course measures and QR can assess quality. Combining multiple measures reduces misclassification.

Advances in knowledge

A new automated quality control method was developed, which trained machine learning classifiers using QR results.",,doi:https://doi.org/10.1259/bjr.20201465; html:https://europepmc.org/articles/PMC10161906; pdf:https://europepmc.org/articles/PMC10161906?pdf=render 33050951,https://doi.org/10.1186/s12916-020-01789-2,Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.,"van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.",,BMC medicine,2020,2020-10-14,Y,Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

We predicted median symptomatic attack rates over the first 12 months of 23% (Niger) to 42% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.

Conclusions

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.",,doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render 33480434,https://doi.org/10.1093/pubmed/fdaa267,"Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.","Gruer LD, Cézard GI, Wallace LA, Hutchinson SJ, Douglas AF, Buchanan D, Katikireddi SV, Millard AD, Goldberg DJ, Sheikh A, Bhopal RS.",,"Journal of public health (Oxford, England)",2022,2022-03-01,Y,Infectious disease; epidemiology; Ethnicity,,,"

Background

Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection.

Methods

We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses.

Results

We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans.

Conclusions

Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.",,doi:https://doi.org/10.1093/pubmed/fdaa267; html:https://europepmc.org/articles/PMC7928762; pdf:https://europepmc.org/articles/PMC7928762?pdf=render @@ -519,8 +519,8 @@ PMC10464868,https://doi.org/,An overview of synthetic administrative data for re 36929968,https://doi.org/10.1016/s0140-6736(22)02235-8,Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.,"Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,"Lancet (London, England)",2022,2022-11-24,Y,,,,"

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.",,doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render 34261639,https://doi.org/10.1136/bmj.n1592,Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform.,"Williamson EJ, McDonald HI, Bhaskaran K, Walker AJ, Bacon S, Davy S, Schultze A, Tomlinson L, Bates C, Ramsay M, Curtis HJ, Forbes H, Wing K, Minassian C, Tazare J, Morton CE, Nightingale E, Mehrkar A, Evans D, Inglesby P, MacKenna B, Cockburn J, Rentsch CT, Mathur R, Wong AYS, Eggo RM, Hulme W, Croker R, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Smeeth L, Goldacre B, Kuper H.",,BMJ (Clinical research ed.),2021,2021-07-14,Y,,,,"

Objective

To assess the association between learning disability and risk of hospital admission and death from covid-19 in England among adults and children.

Design

Population based cohort study on behalf of NHS England using the OpenSAFELY platform.

Setting

Patient level data were obtained for more than 17 million people registered with a general practice in England that uses TPP software. Electronic health records were linked with death data from the Office for National Statistics and hospital admission data from NHS Secondary Uses Service.

Participants

Adults (aged 16-105 years) and children (<16 years) from two cohorts: wave 1 (registered with a TPP practice as of 1 March 2020 and followed until 31 August 2020); and wave 2 (registered 1 September 2020 and followed until 8 February 2021). The main exposure group consisted of people on a general practice learning disability register; a subgroup was defined as those having profound or severe learning disability. People with Down's syndrome and cerebral palsy were identified (whether or not they were on the learning disability register).

Main outcome measure

Covid-19 related hospital admission and covid-19 related death. Non-covid-19 deaths were also explored.

Results

For wave 1, 14 312 023 adults aged ≥16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a covid-19 related hospital admission; there were 222 (0.25%) covid-19 related deaths and 602 (0.7%) non-covid deaths. Among adults not on the register, 29 781 (0.2%) had a covid-19 related hospital admission; there were 13 737 (0.1%) covid-19 related deaths and 69 837 (0.5%) non-covid deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for covid-19 related hospital admission and 8.2 (7.2 to 9.4) for covid-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down's syndrome and cerebral palsy were associated with increased hazards for both events; Down's syndrome to a greater extent. Hazard ratios for non-covid deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but covid-19 related deaths and hospital admissions were rare, reflecting low event rates among children.

Conclusions

People with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Prompt access to covid-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for covid-19 vaccination and other targeted preventive measures should be considered.",,doi:https://doi.org/10.1136/bmj.n1592; html:https://europepmc.org/articles/PMC8278652; pdf:https://europepmc.org/articles/PMC8278652?pdf=render 34053260,https://doi.org/10.1098/rstb.2020.0283,Exploring surveillance data biases when estimating the reproduction number: with insights into subpopulation transmission of COVID-19 in England.,"Sherratt K, Abbott S, Meakin SR, Hellewell J, Munday JD, Bosse N, CMMID COVID-19 Working Group, Jit M, Funk S.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Transmission; Surveillance; Bias; Covid-19; Sars-cov-2; Time-varying Reproduction Number,,,"The time-varying reproduction number (Rt: the average number of secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of Rt estimates to different data sources representing COVID-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions and deaths with confirmed COVID-19 in seven regions of England over March through August 2020. We estimated Rt using a model that mapped unobserved infections to each data source. We then compared differences in Rt with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. Rt estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of the disease. We highlight that policy makers could better target interventions by considering the source populations of Rt estimates. Further work should clarify the best way to combine and interpret Rt estimates from different data sources based on the desired use. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0283; html:https://europepmc.org/articles/PMC8165604; pdf:https://europepmc.org/articles/PMC8165604?pdf=render -35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Biomedical Ontologies; Data Accuracy; Covid-19; Sars-cov-2; Long Covid; Post–covid-19 Syndrome; Data Extracts; Post–acute Covid-19 Syndrome,,,"

Background

Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.

Objective

We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.

Methods

We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.

Results

In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).

Conclusions

The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859 33299071,https://doi.org/10.1038/s41746-020-00357-5,Belief of having had unconfirmed Covid-19 infection reduces willingness to participate in app-based contact tracing.,"Bachtiger P, Adamson A, Quint JK, Peters NS.",,NPJ digital medicine,2020,2020-11-06,Y,,,,"Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). The UK National Health Service (NHS) Track and Trace Service has plans for a nationwide app that notifies the need for self-isolation to those in contact with a person testing positive for COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. The objective of this study was to measure the determinants of willingness to participate in an NHS app-based contact-tracing programme using a questionnaire within the Care Information Exchange (CIE)-the largest patient-facing electronic health record in the NHS. Among 47,708 registered NHS users of the CIE, 27% completed a questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation-related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded 'no', 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact-tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48-0.67]; OR for 3-4/10 = 0.744 [CI 0.64-0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585-0.908]). In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing over an appropriate age range is 60%-close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact tracing to be an effective intervention to help suppress an epidemic. Difficulty comprehending government advice and uncertainty of diagnosis, based on a public health policy of not testing to confirm self-reported COVID-19 infection during lockdown, therefore reduce willingness to adopt a government contact-tracing app to a level below the threshold for effectiveness as a tool to suppress an epidemic.",,doi:https://doi.org/10.1038/s41746-020-00357-5; html:https://europepmc.org/articles/PMC7648058; pdf:https://europepmc.org/articles/PMC7648058?pdf=render +35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Biomedical Ontologies; Data Accuracy; Covid-19; Sars-cov-2; Long Covid; Post–covid-19 Syndrome; Data Extracts; Post–acute Covid-19 Syndrome,,,"

Background

Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.

Objective

We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.

Methods

We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.

Results

In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).

Conclusions

The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859 37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render 34053271,https://doi.org/10.1098/rstb.2020.0266,Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection.,"Jombart T, Ghozzi S, Schumacher D, Taylor TJ, Leclerc QJ, Jit M, Flasche S, Greaves F, Ward T, Eggo RM, Nightingale E, Meakin S, Brady OJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley GF, Höhle M, Edmunds WJ.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Algorithm; Surveillance; outbreak; Machine Learning; Asmodee; Trendbreaker,,,"As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0266; html:https://europepmc.org/articles/PMC8165581; pdf:https://europepmc.org/articles/PMC8165581?pdf=render 37358897,https://doi.org/10.2196/45849,Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.,"Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.",,JMIR formative research,2023,2023-06-26,Y,Pain; Mental health; Annotation; Information Extraction; Natural Language Processing,,,"

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.",,doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render; doi:https://doi.org/10.2196/45849 @@ -559,7 +559,7 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render 33075408,https://doi.org/10.1016/j.jaci.2020.10.007,Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.,"Mahil SK, Dand N, Mason KJ, Yiu ZZN, Tsakok T, Meynell F, Coker B, McAteer H, Moorhead L, Mackenzie T, Rossi MT, Rivera R, Mahe E, Carugno A, Magnano M, Rech G, Balogh EA, Feldman SR, De La Cruz C, Choon SE, Naldi L, Lambert J, Spuls P, Jullien D, Bachelez H, McMahon DE, Freeman EE, Gisondi P, Puig L, Warren RB, Di Meglio P, Langan SM, Capon F, Griffiths CEM, Barker JN, Smith CH, PsoProtect study group.",,The Journal of allergy and clinical immunology,2021,2020-10-16,Y,Psoriasis; Immunosuppressants; risk factors; Hospitalization; Biologics; Covid-19,,,"

Background

The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective

Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods

Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors.

Results

Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94).

Conclusion

In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.",,doi:https://doi.org/10.1016/j.jaci.2020.10.007; html:https://europepmc.org/articles/PMC7566694; pdf:https://europepmc.org/articles/PMC7566694?pdf=render; pdf:http://www.jacionline.org/article/S0091674920314135/pdf 37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x -33623826,https://doi.org/10.12688/wellcomeopenres.16164.2,"The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study.","Leng T, White C, Hilton J, Kucharski A, Pellis L, Stage H, Davies NG, Centre for Mathematical Modelling of Infectious Disease 2019 nCoV Working Group, Keeling MJ, Flasche S.",,Wellcome open research,2020,2020-01-01,Y,Exit Strategy; Covid-19; Contact Clustering; Social Bubble,,,"Background: ​ During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: ​ We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. Results:  Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. Conclusions: ​ If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.",,doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render +33623826,https://doi.org/10.12688/wellcomeopenres.16164.2,"The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study.","Leng T, White C, Hilton J, Kucharski A, Pellis L, Stage H, Davies NG, Centre for Mathematical Modelling of Infectious Disease 2019 nCoV Working Group, Keeling MJ, Flasche S.",,Wellcome open research,2020,2020-01-01,Y,Exit Strategy; Covid-19; Contact Clustering; Social Bubble,,,"Background: ​ During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: ​ We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. Results:  Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. Conclusions: ​ If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.",,doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render; doi:https://doi.org/10.12688/wellcomeopenres.16164.2 37433797,https://doi.org/10.1038/s41467-023-38816-8,The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom.,"Brand SPC, Cavallaro M, Cumming F, Turner C, Florence I, Blomquist P, Hilton J, Guzman-Rincon LM, House T, Nokes DJ, Keeling MJ.",,Nature communications,2023,2023-07-11,Y,,,,"Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.",,doi:https://doi.org/10.1038/s41467-023-38816-8; html:https://europepmc.org/articles/PMC10336136; pdf:https://europepmc.org/articles/PMC10336136?pdf=render 36084076,https://doi.org/10.1371/journal.pone.0273687,"""The vaccination is positive; I don't think it's the panacea"": A qualitative study on COVID-19 vaccine attitudes among ethnically diverse healthcare workers in the United Kingdom.","Gogoi M, Wobi F, Qureshi I, Al-Oraibi A, Hassan O, Chaloner J, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,PloS one,2022,2022-09-09,Y,,,,"

Background

Globally, healthcare workers (HCWs) were prioritised for receiving vaccinations against the coronavirus disease-2019 (COVID-19). Previous research has shown disparities in COVID-19 vaccination uptake among HCWs based on ethnicity, job role, sex, age, and deprivation. However, vaccine attitudes underpinning these variations and factors influencing these attitudes are yet to be fully explored.

Methods

We conducted a qualitative study with 164 HCWs from different ethnicities, sexes, job roles, migration statuses, and regions in the United Kingdom (UK). Interviews and focus groups were conducted online or telephonically, and recorded with participants' permission. Recordings were transcribed and a two-pronged analytical approach was adopted: content analysis for categorising vaccine attitudes and thematic analysis for identifying factors influencing vaccine attitudes.

Findings

We identified four different COVID-19 vaccine attitudes among HCWs: Active Acceptance, Passive Acceptance, Passive Decline, and Active Decline. Content analysis of the transcripts showed that HCWs from ethnic minority communities and female HCWs were more likely to either decline (actively/passively) or passively accept vaccination-reflecting hesitancy. Factors influencing these attitudes included: trust; risk perception; social influences; access and equity; considerations about the future.

Interpretation

Our data show that attitudes towards COVID-19 vaccine are diverse, and elements of hesitancy may persist even after uptake. This has implications for the sustainability of the COVID-19 vaccine programme, particularly as new components (for example boosters) are being offered. We also found that vaccine attitudes differed by ethnicity, sex and job role, which calls for an intersectional and dynamic approach for improving vaccine uptake among HCWs. Trust, risk perception, social influences, access and equity and future considerations all influence vaccine attitudes and have a bearing on HCWs' decision about accepting or declining the COVID-19 vaccine. Based on our findings, we recommend building trust, addressing structural inequities and, designing inclusive and accessible information to address hesitancy.",,doi:https://doi.org/10.1371/journal.pone.0273687; html:https://europepmc.org/articles/PMC9462779; pdf:https://europepmc.org/articles/PMC9462779?pdf=render 34148732,https://doi.org/10.1016/j.bja.2021.05.001,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,British journal of anaesthesia,2021,2021-06-18,Y,Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19,,,"

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.",,doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render @@ -571,7 +571,7 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35337642,https://doi.org/10.1016/s2589-7500(22)00018-8,"Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.","Närhi F, Moonesinghe SR, Shenkin SD, Drake TM, Mulholland RH, Donegan C, Dunning J, Fairfield CJ, Girvan M, Hardwick HE, Ho A, Leeming G, Nguyen-Van-Tam JS, Pius R, Russell CD, Shaw CA, Spencer RG, Turtle L, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, Docherty AB, ISARIC4C investigators.",,The Lancet. Digital health,2022,2022-04-01,Y,,,,"

Background

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods

We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.

Findings

Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021.

Interpretation

Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.

Funding

UK National Institute for Health Research and UK Medical Research Council.",,doi:https://doi.org/10.1016/S2589-7500(22)00018-8; html:https://europepmc.org/articles/PMC8940185; pdf:http://www.thelancet.com/article/S2589750022000188/pdf 37321240,https://doi.org/10.1016/s2215-0366(23)00113-x,Mental health in Europe during the COVID-19 pandemic: a systematic review.,"Ahmed N, Barnett P, Greenburgh A, Pemovska T, Stefanidou T, Lyons N, Ikhtabi S, Talwar S, Francis ER, Harris SM, Shah P, Machin K, Jeffreys S, Mitchell L, Lynch C, Foye U, Schlief M, Appleton R, Saunders KRK, Baldwin H, Allan SM, Sheridan-Rains L, Kharboutly O, Kular A, Goldblatt P, Stewart R, Kirkbride JB, Lloyd-Evans B, Johnson S.",,The lancet. Psychiatry,2023,2023-06-12,Y,,,,"The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions.",,doi:https://doi.org/10.1016/S2215-0366(23)00113-X; html:https://europepmc.org/articles/PMC10259832; pdf:https://europepmc.org/articles/PMC10259832?pdf=render 34965929,https://doi.org/10.1136/bmj-2021-065834,GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.,"Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.",,BMJ (Clinical research ed.),2021,2021-12-29,Y,,,,"

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.",,doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render -36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render +36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf 34716166,https://doi.org/10.1136/bmjopen-2021-053268,Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care.,"De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths C.",,BMJ open,2021,2021-10-29,Y,Asthma; Respiratory Medicine (See Thoracic Medicine); Paediatric Thoracic Medicine,,,"

Objective

To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications.

Methods

Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework.

Participants

Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit.

Results

10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers.

Conclusions

An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma. A pilot randomised controlled trial is warranted to better estimate the effect size on adherence, with improved technical support for the EMD.",,doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render 36936594,https://doi.org/10.1136/bmjmed-2022-000247,Measuring multimorbidity in research: Delphi consensus study.,"Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",,BMJ medicine,2022,2022-07-27,Y,Medicine; epidemiology; Primary Health Care; Public Health; Research Design,,,"

Objective

To develop international consensus on the definition and measurement of multimorbidity in research.

Design

Delphi consensus study.

Setting

International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.

Participants

Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.

Results

150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.

Conclusions

Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",,doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render 35866236,https://doi.org/10.7189/jogh.12.05033,The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.,"Doubova SV, Arsenault C, Contreras-Sánchez SE, Borrayo-Sánchez G, Leslie HH.",,Journal of global health,2022,2022-07-23,Y,,,,"

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR = 1.15, 95%CI = 1.11-1.19) with a growing trend over time (IRR = 1.04, 95%CI = 1.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.",,doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render @@ -586,18 +586,18 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35726508,https://doi.org/10.1177/10398562221103117,Improving quantification of anticholinergic burden using the Anticholinergic Effect on Cognition Scale - a healthcare improvement study in a geriatric ward setting.,"Balasundaram B, Ang WST, Stewart R, Bishara D, Ooi CH, Li F, Akram F, Eu Kwek AB.",,Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists,2022,2022-06-21,Y,Dementia; Delirium; Anticholinergic drugs; Anticholinergic Burden Scales; Anticholinergic Effect On Cognition Scale,,,"

Objective

Anticholinergic burden refers to the cumulative effects of taking multiple medications with anticholinergic effects. This study was carried out in a public hospital in Singapore, aimed to improve and achieve a 100% comprehensive identification and review of measured, anticholinergic burden in a geriatric psychiatry liaison service to geriatric wards. We evaluated changes in pre-to post-assessment anticholinergic burden scores and trainee feedback.

Method

Plan Do Study Act methodology was employed, and Anticholinergic Effect on Cognition scale (AEC) was implemented as the study intervention. A survey instrument evaluated trainee feedback.

Results

There was no measured anticholinergic burden in a baseline of 170 assessments. 75 liaison psychiatry assessments were conducted between June and November 2021 in two cycles. 94.7% of pre-assessments (at the time of assessment) and 71.1% of post-assessments (following assessment) had a record of AEC scores in clinical documentation in cycle one, improving in the second cycle to 100%, 94.6%, respectively. A high post-assessment AEC score of 3 and over reduced from 15.8% in cycle one to 5.4% in cycle two. The trainee feedback suggested an enriching educational experience.

Conclusions

Using the AEC scale, the findings support the feasibility of comprehensive identification and review of measured anticholinergic burden in older people with neurocognitive disorders.",,doi:https://doi.org/10.1177/10398562221103117; html:https://europepmc.org/articles/PMC9379386; pdf:https://europepmc.org/articles/PMC9379386?pdf=render 35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render; pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf 33500288,https://doi.org/10.1136/bmjopen-2020-042945,Hospital bed capacity and usage across secondary healthcare providers in England during the first wave of the COVID-19 pandemic: a descriptive analysis.,"Mateen BA, Wilde H, Dennis JM, Duncan A, Thomas N, McGovern A, Denaxas S, Keeling M, Vollmer S.",,BMJ open,2021,2021-01-26,Y,Public Health; Health Policy; Intensive & Critical Care; Covid-19,,,"

Objective

In this study, we describe the pattern of bed occupancy across England during the peak of the first wave of the COVID-19 pandemic.

Design

Descriptive survey.

Setting

All non-specialist secondary care providers in England from 27 March27to 5 June 2020.

Participants

Acute (non-specialist) trusts with a type 1 (ie, 24 hours/day, consultant-led) accident and emergency department (n=125), Nightingale (field) hospitals (n=7) and independent sector secondary care providers (n=195).

Main outcome measures

Two thresholds for 'safe occupancy' were used: 85% as per the Royal College of Emergency Medicine and 92% as per NHS Improvement.

Results

At peak availability, there were 2711 additional beds compatible with mechanical ventilation across England, reflecting a 53% increase in capacity, and occupancy never exceeded 62%. A consequence of the repurposing of beds meant that at the trough there were 8.7% (8508) fewer general and acute beds across England, but occupancy never exceeded 72%. The closest to full occupancy of general and acute bed (surge) capacity that any trust in England reached was 99.8% . For beds compatible with mechanical ventilation there were 326 trust-days (3.7%) spent above 85% of surge capacity and 154 trust-days (1.8%) spent above 92%. 23 trusts spent a cumulative 81 days at 100% saturation of their surge ventilator bed capacity (median number of days per trust=1, range: 1-17). However, only three sustainability and transformation partnerships (aggregates of geographically co-located trusts) reached 100% saturation of their mechanical ventilation beds.

Conclusions

Throughout the first wave of the pandemic, an adequate supply of all bed types existed at a national level. However, due to an unequal distribution of bed utilisation, many trusts spent a significant period operating above 'safe-occupancy' thresholds despite substantial capacity in geographically co-located trusts, a key operational issue to address in preparing for future waves.",,doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?pdf=render -37596262,https://doi.org/10.1038/s41467-023-40679-y,A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.,"Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ.",,Nature communications,2023,2023-08-18,Y,,,,"Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.",,doi:https://doi.org/10.1038/s41467-023-40679-y; html:https://europepmc.org/articles/PMC10439125; pdf:https://europepmc.org/articles/PMC10439125?pdf=render 37159441,https://doi.org/10.1371/journal.pdig.0000218,Hospital-wide natural language processing summarising the health data of 1 million patients.,"Bean DM, Kraljevic Z, Shek A, Teo J, Dobson RJB.",,PLOS digital health,2023,2023-05-09,Y,,,,"Electronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR's try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King's College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.",,doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render; doi:https://doi.org/10.1371/journal.pdig.0000218 +37596262,https://doi.org/10.1038/s41467-023-40679-y,A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.,"Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ.",,Nature communications,2023,2023-08-18,Y,,,,"Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.",,doi:https://doi.org/10.1038/s41467-023-40679-y; html:https://europepmc.org/articles/PMC10439125; pdf:https://europepmc.org/articles/PMC10439125?pdf=render 35443953,https://doi.org/10.1136/bmjopen-2021-056523,Can we accurately forecast non-elective bed occupancy and admissions in the NHS? A time-series MSARIMA analysis of longitudinal data from an NHS Trust.,"Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",,BMJ open,2022,2022-04-20,Y,epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine,,,"

Objectives

The main objective of the study was to develop more accurate and precise short-term forecasting models for admissions and bed occupancy for an NHS Trust located in Bristol, England. Subforecasts for the medical and surgical specialties, and for different lengths of stay were realised DESIGN: Autoregressive integrated moving average models were specified on a training dataset of daily count data, then tested on a 6-week forecast horizon. Explanatory variables were included in the models: day of the week, holiday days, lagged temperature and precipitation.

Setting

A secondary care hospital in an NHS Trust in South West England.

Participants

Hospital admissions between September 2016 and March 2020, comprising 1291 days.

Primary and secondary outcome measures

The accuracy of the forecasts was assessed through standard measures, as well as compared with the actual data using accuracy thresholds of 10% and 20% of the mean number of admissions or occupied beds.

Results

The overall Autoregressive Integrated Moving Average (ARIMA) admissions forecast was compared with the Trust's forecast, and found to be more accurate, namely, being closer to the actual value 95.6% of the time. Furthermore, it was more precise than the Trust's. The subforecasts, as well as those for bed occupancy, tended to be less accurate compared with the overall forecasts. All of the explanatory variables improved the forecasts.

Conclusions

ARIMA models can forecast non-elective admissions in an NHS Trust accurately on a 6-week horizon, which is an improvement on the current predictive modelling in the Trust. These models can be readily applied to other contexts, improving patient flow.",,doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render 36036238,https://doi.org/10.1002/clt2.12180,Mixed-methods evaluation of a nurse-led allergy clinic model in primary care: Feasibility trial.,"Hammersley V, Kelman M, Morrice L, Kendall M, Mukerjhee M, Harley S, Schwarze J, Sheikh A.",,Clinical and translational allergy,2022,2022-08-01,Y,Allergy; Quality of life; Primary Care,,,"

Introduction

It is now widely acknowledged that there are serious shortcomings in allergy care provision for patients seen in primary care. We sought to assess the feasibility of delivering and evaluating a new nurse-led allergy service in primary care, measured by recruitment, retention and estimates of the potential impact of the intervention on disease-specific quality of life.

Methods

Mixed-methods evaluation of a nurse-led primary care-based allergy clinic in Edinburgh, UK undertaken during the period 2017-2021 with a focus on suspected food allergy and atopic eczema in young children, allergic rhinitis in children and young people, and suspected anaphylaxis in adults. Prior to March 2020, patients were seen face-to-face (Phase 1). Due to COVID-19 pandemic restrictions, recruitment was halted between March-August 2020, and a remote clinic was restarted in September 2020 (Phase 2). Disease-specific quality of life was measured at baseline and 6-12 weeks post intervention using validated instruments. Quantitative data were descriptively analysed. We undertook interviews with 16 carers/patients and nine healthcare professionals, which were thematically analysed.

Results

During Phase 1, 426/506 (84%) referred patients met the eligibility criteria; 40/46 (87%) of Phase 2 referrals were eligible. Males and females were recruited in approximately equal numbers. The majority (83%) of referrals were for possible food allergy or anaphylaxis. Complete data were available for 338/426 (79%) patients seen in Phase 1 and 30/40 (75%) in Phase 2. Compared with baseline assessments, there were improvements in disease-specific quality of life for most categories of patients. Patients/carers and healthcare professionals reported high levels of satisfaction, this being reinforced by the qualitative interviews in which convenience and speed of access to expert opinion, the quality of the consultation, and patient/care empowerment were particularly emphasised.

Conclusion

This large feasibility trial has demonstrated that it is possible to recruit, deliver and retain individuals into a nurse-led allergy clinic with both face-to-face and remote consultations. Our data indicate that the intervention was considered acceptable to patients/carers and healthcare professionals. The before-after data of disease-specific quality of life suggest that the intervention may prove effective, but this now needs to be confirmed through a formal randomised controlled trial.

Trial registration

ClinicalTrials.gov reference NCT03826953.",,doi:https://doi.org/10.1002/clt2.12180; html:https://europepmc.org/articles/PMC9362986; pdf:https://europepmc.org/articles/PMC9362986?pdf=render -36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276; doi:https://doi.org/10.1016/s2214-109x(23)00007-4 33934335,https://doi.org/10.1111/anae.15466,Long-term trends in critical care admissions in Wales*. ,"Pugh RJ, Bailey R, Szakmany T, Al Sallakh M, Hollinghurst J, Akbari A, Griffiths R, Battle C, Thorpe C, Subbe CP, Lyons RA.",,Anaesthesia,2021,2021-05-02,Y,,,,"As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.",,doi:https://doi.org/10.1111/anae.15466; html:https://europepmc.org/articles/PMC10138728; pdf:https://europepmc.org/articles/PMC10138728?pdf=render; pdf:https://cronfa.swan.ac.uk/Record/cronfa56830/Download/56830__24941__ed34d96421c74ecca52d5a3aaf9afc85.pdf +36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276; doi:https://doi.org/10.1016/s2214-109x(23)00007-4 35301688,https://doi.org/10.1007/s12471-022-01670-2,Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.,"van de Leur RR, Bleijendaal H, Taha K, Mast T, Gho JMIH, Linschoten M, van Rees B, Henkens MTHM, Heymans S, Sturkenboom N, Tio RA, Offerhaus JA, Bor WL, Maarse M, Haerkens-Arends HE, Kolk MZH, van der Lingen ACJ, Selder JJ, Wierda EE, van Bergen PFMM, Winter MM, Zwinderman AH, Doevendans PA, van der Harst P, Pinto YM, Asselbergs FW, van Es R, Tjong FVY, CAPACITY-COVID collaborative consortium.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2022,2022-03-17,Y,Mortality; Electrocardiogram; Arrhythmia; Machine Learning; Deep Learning; Covid-19,,,"

Background and purpose

The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients.

Methods

Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation.

Results

Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block.

Conclusion

This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.",,doi:https://doi.org/10.1007/s12471-022-01670-2; html:https://europepmc.org/articles/PMC8929464; pdf:https://europepmc.org/articles/PMC8929464?pdf=render 35908569,https://doi.org/10.1016/s0140-6736(22)01109-6,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-07-01,Y,,,,"

Background

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

Methods

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

Findings

Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render; pdf:http://www.thelancet.com/article/S0140673622011096/pdf 36777997,https://doi.org/10.1016/j.xgen.2022.100181,Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.,"Partanen JJ, Häppölä P, Zhou W, Lehisto AA, Ainola M, Sutinen E, Allen RJ, Stockwell AD, Leavy OC, Oldham JM, Guillen-Guio B, Cox NJ, Hirbo JB, Schwartz DA, Fingerlin TE, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV, Ripatti S, Pirinen M, International IPF Genetics Consortium, Global Biobank Meta-Analysis Initiative (GBMI), Laitinen T, Kaarteenaho R, Myllärniemi M, Daly MJ, Koskela JT.",,Cell genomics,2022,2022-10-12,Y,Meta-analysis; idiopathic pulmonary fibrosis; Gwas; Ancestry; Muc5b; Fine-mapping; Cross-population Analysis; Covid-19; Global Biobank Meta-Analysis Initiative,,,"The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.",,doi:https://doi.org/10.1016/j.xgen.2022.100181; html:https://europepmc.org/articles/PMC9903787; pdf:https://europepmc.org/articles/PMC9903787?pdf=render; pdf:https://helda.helsinki.fi/bitstream/10138/355828/1/Leveraging_global_multi_ancestry_meta_a...pdf 35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render -35802687,https://doi.org/10.1371/journal.pone.0270668,"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.","Godolphin PJ, Fisher DJ, Berry LR, Derde LPG, Diaz JV, Gordon AC, Lorenzi E, Marshall JC, Murthy S, Shankar-Hari M, Sterne JAC, Tierney JF, Vale CL.",,PloS one,2022,2022-07-08,Y,,,,"

Background

A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.

Methods

Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.

Findings

One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.

Conclusions

Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.",,doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable 34240696,https://doi.org/10.2807/1560-7917.es.2021.26.27.2000004,"Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season. ","Xu Y, Lewandowski K, Downs LO, Kavanagh J, Hender T, Lumley S, Jeffery K, Foster D, Sanderson ND, Vaughan A, Morgan M, Vipond R, Carroll M, Peto T, Crook D, Walker AS, Matthews PC, Pullan ST.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-07-01,Y,,,,"BackgroundInfluenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions.AimTo evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.MethodsWe conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.ResultsCompared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.ConclusionNanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.",,doi:https://doi.org/10.2807/1560-7917.ES.2021.26.27.2000004; html:https://europepmc.org/articles/PMC8268652; pdf:https://europepmc.org/articles/PMC8268652?pdf=render +35802687,https://doi.org/10.1371/journal.pone.0270668,"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.","Godolphin PJ, Fisher DJ, Berry LR, Derde LPG, Diaz JV, Gordon AC, Lorenzi E, Marshall JC, Murthy S, Shankar-Hari M, Sterne JAC, Tierney JF, Vale CL.",,PloS one,2022,2022-07-08,Y,,,,"

Background

A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.

Methods

Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.

Findings

One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.

Conclusions

Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.",,doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable 34319235,https://doi.org/10.2196/28873,Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH): Protocol for a Prospective Observational Study.,"Ranjan Y, Althobiani M, Jacob J, Orini M, Dobson RJ, Porter J, Hurst J, Folarin AA.",,JMIR research protocols,2021,2021-10-07,Y,Lung diseases; Mental health; Remote Monitoring; Respiratory Health; Internet Of Things; Mhealth; Mobile Health; Wearables; Covid-19; Cardiopulmonary Diseases,,,"

Background

Chronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.

Objective

The primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.

Methods

Twenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.

Results

The Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.

Conclusions

The RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.

Trial registration

ISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601.

International registered report identifier (irrid)

PRR1-10.2196/28873.",,doi:https://doi.org/10.2196/28873; html:https://europepmc.org/articles/PMC8500349 37043172,https://doi.org/10.1007/s12325-023-02511-3,Commentary: Patient Perspectives on Artificial Intelligence; What have We Learned and How Should We Move Forward?,"Camaradou JCL, Hogg HDJ.",,Advances in therapy,2023,2023-04-12,Y,Development; Artificial intelligence; Technology; Product; Clinical; Innovation; Patient; Perspectives; Engagement; Involvement; Acceptability; Public; Start-ups; Small Medium-sized Enterprises; Multi-stakeholder,,,"Artificial intelligence (AI) in healthcare has now begun to make its contributions to real-world patient care with varying degrees of both public and clinical acceptability around it. The heavy investment from governments, industry and academia needed to reach this point has helped to surface different perspectives on AI. As clinical AI applications become a reality, however, there is an increasing need to harness and integrate patient perspectives, which address the distinct needs of different populations, healthcare systems and clinical problems more closely. Despite this need, patient perspectives on AI implementation have little presence in academic literature and within implementation science and are not sufficiently considered throughout the MedTech and eHealthtech product development cycle, which brings its own challenges and opportunities. This joint patient expert/clinician commentary aims to briefly summarise views on AI. It reflects upon recommendations on how stakeholders such as clinicians and Health & MedTech small and medium-sized enterprises (SMEs) can make practical usage of these views. The recommendations of the authors centre around how to work better with patients to enable both product centric and patient centric innovation and person-centred care.",,doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf 36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/S2589-7500(22)00151-0; doi:https://doi.org/10.1016/s2589-7500(22)00151-0 @@ -621,6 +621,7 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35765786,https://doi.org/10.7189/jogh.12.04052,"Global, regional, and national prevalence of asthma in 2019: a systematic analysis and modelling study.","Song P, Adeloye D, Salim H, Dos Santos JP, Campbell H, Sheikh A, Rudan I.",,Journal of global health,2022,2022-06-29,Y,,,,"

Background

Asthma has a significant impact on people of all ages, particularly children. A lack of universally accepted case definition and confirmatory tests and a poor understanding of major risks interfere with a global response. We aimed to provide global estimates of asthma prevalence and cases in 2019 across four main epidemiological case definitions - current wheezing, ever wheezing, current asthma, and ever asthma. We further investigated major associated factors to determine regional and national distributions of prevalence and cases for current wheezing and ever asthma.

Methods

We identified relevant population-based studies published between January 1, 1990, and December 31, 2019. Using a multilevel multivariable mixed-effects meta-regression model, we assessed the age- and sex-adjusted associations of asthma with study-level variables, including year, setting, region and socio-demographic index (SDI). Using a random-effects meta-analysis, we then identified risk factors for current wheezing and asthma. From a ""risk factor-based model"", which included current smoking, and biomass exposure for current wheezing, and rural setting, current smoking, biomass exposure, and SDI for ever asthma, we estimated case numbers and prevalence across regions and 201 countries and territories in 2019.

Results

220 population-based studies conducted in 88 countries were retained. In 2019, the global prevalence estimates of asthma in people aged 5-69 years by various definitions, namely current wheezing, ever wheezing, current asthma, and ever asthma were 11.5% (95% confidence interval (CI) = 9.1-14.3), 17.9% (95% CI = 14.2-22.3), 5.4% (95% CI = 3.2-9.0) and 9.8% (95% CI = 7.8-12.2), respectively. These translated to 754.6 million (95% CI = 599. 7-943.4), 1181.3 million (95% CI = 938.0-1,471.0), 357.4 million (95% CI = 213.0-590.8), 645.2 million (95% CI = 513.1-806.2) cases, respectively. The overall prevalence of current wheezing among people aged 5-69 years was the highest in the African Region at 13.2% (95% CI = 10.5-16.5), and the lowest in the Americas Region at 10.0% (95% CI = 8.0-12.5). For ever asthma, the estimated prevalence in those aged 5-69 years was also the highest in the African Region at 11.3% (95% CI = 9.0-14.1), but the lowest in South-East Asia Region (8.8, 95% CI = 7.0-11.0).

Conclusions

Although varying approaches to case identification in different settings make epidemiological estimates of asthma very difficult, this analysis reaffirms asthma as a common global respiratory condition before the COVID-19 pandemic in 2019, with higher prevalence than previously reported in many world settings.",,doi:https://doi.org/10.7189/jogh.12.04052; html:https://europepmc.org/articles/PMC9239324; pdf:https://europepmc.org/articles/PMC9239324?pdf=render PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm during the COVID-19 pandemic: a repeat cross-sectional UK population survey","John A, Lee S, Solomon S, Crepaz-Keay D, McDaid S, Morton A, Davidson G, Van Bortel T, Kousoulis A.",,BMJ open,2021,2021-01-01,Y,Mental health; Public Health; Suicide & Self-harm; Covid-19,,,"

Objectives

There has been speculation on the impact of the COVID-19 pandemic and the associated lockdown on suicidal thoughts and self-harm and the factors associated with any change. We aimed to assess the effects and change in effects of risk factors including loneliness and coping, as well as pre-existing mental health conditions on suicidal thoughts and self-harm during the COVID-19 pandemic.

Design

This study was a repeated cross-sectional online population-based survey.

Participants and measures

Non-probability quota sampling was adopted on the UK adult population and four waves of data were analysed during the pandemic (17 March 2020 to 29 May 2020). Outcomes were suicidal thoughts and self-harm associated with the pandemic while loneliness, coping, pre-existing mental health conditions, employment status and demographics were covariates. We ran binomial regressions to evaluate the adjusted risks of the studied covariates as well as the changes in effects over time.

Results

The proportion of individuals who felt lonely increased sharply from 9.8% to 23.9% after the UK lockdown began. Young people (aged 18–24 years), females, students, those who were unemployed and individuals with pre-existing mental health conditions were more likely to report feeling lonely and not coping well. 7.7%–10.0% and 1.9%–2.2% of respondents reported having suicidal thoughts and self-harm associated with the pandemic respectively throughout the period studied. Results from cross-tabulation and adjusted regression analyses showed young adults, coping poorly and with pre-existing mental health conditions were significantly associated with suicidal thoughts and self-harm. Loneliness was significantly associated with suicidal thoughts but not self-harm.

Conclusions

The association between suicidality, loneliness and coping was evident in young people during the early stages of the pandemic. Developing effective interventions designed and coproduced to address loneliness and promote coping strategies during prolonged social isolation may promote mental health and help mitigate suicidal thoughts and self-harm associated with the pandemic.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8718341; pdf:https://europepmc.org/articles/PMC8718341?pdf=render 35923560,https://doi.org/10.1016/j.lanepe.2022.100475,Equity of access to NHS-funded hip replacements in England and Wales: Trends from 2006 to 2016.,"Wyatt S, Bailey R, Moore P, Revell M.",,The Lancet regional health. Europe,2022,2022-07-29,Y,trends; Equity; Hip Replacements; Socio-economic Deprivation,,,"

Background

Elective hip replacement is a cost-effective means of improving hip function. Previous research has suggested that the supply of hip replacements in the NHS is governed by the inverse care law. We examine whether inequities in supply improved in England and Wales between 2006 and 2016.

Methods

We compare levels of need and supply of NHS funded hip replacements to adults aged 50+ years, across quintiles of deprivation in England and Wales between 2006 and 2016. We use data from routine health records and a large longitudinal study and adjust for age and sex using general additive negative-binomial regression.

Findings

The number of NHS-funded hip replacements per 100,000 population rose substantially from 272.6 and 266.7 in 2002, to 539.7 and 466.3 in 2018 in England and Wales respectively. Having adjusted for age and sex, people living in the most deprived quintile were 2.36 (95% CI, 1.69 to 3.29) times more likely to need a hip replacement in 2006 than those living in quintile 3, whereas those living in the least deprived quintile were 0.45 (95% CI, 0.39 to 0.69) as likely. Despite this, people living in the most deprived quintile were 0.81 (95% CI, 0.78 to 0.83) times as likely in England and 0.93 (95% CI, 0.84 to 1.04) as likely in Wales to receive an NHS-funded hip replacement in 2006 than those living in quintile 3. We found no evidence that these substantial inequities had reduced between 2006 and 2016.

Interpretation

With respect to hip-replacement surgery in England and Wales, policy ambitions to reduce healthcare inequities have not been realised.

Funding

This work was supported by Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2022.100475; html:https://europepmc.org/articles/PMC9340533; pdf:https://europepmc.org/articles/PMC9340533?pdf=render +37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,Y,Depression; Mobile phone; Missing Data; Smartphones; Mobile Health; Wearable Devices; Behavioral Patterns; Digital Phenotypes,,,"

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088; pdf:https://www.jmir.org/2023/1/e45233/PDF 35835543,https://doi.org/10.1136/heartjnl-2022-321196,Eligibility for early rhythm control in patients with atrial fibrillation in the UK Biobank.,"Kany S, Cardoso VR, Bravo L, Williams JA, Schnabel R, Fabritz L, Gkoutos GV, Kirchhof P.",,Heart (British Cardiac Society),2022,2022-11-10,Y,Atrial fibrillation; Stroke; Catheter ablation,,,"

Objective

The Early Treatment of Atrial Fibrillation for Stroke Prevention (EAST-AFNET4) trial showed a clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF). The generalisability of the results in the general population is not known.

Methods

Participants in the population-based UK Biobank were assessed for eligibility based on the EAST-AFNET4 inclusion/exclusion criteria. Treatment of all eligible participants was classified as early rhythm-control (antiarrhythmic drug therapy or AF ablation) or usual care. To assess treatment effects, primary care data and Hospital Episode Statistics were merged with UK Biobank data.Efficacy and safety outcomes were compared between groups in the entire cohort and in a propensity-matched data set.

Results

AF was present in 35 526/502 493 (7.1%) participants, including 8340 (988 with AF <1 year) with AF at enrolment and 27 186 with incident AF during follow-up. Most participants (22 003/27 186; 80.9%) with incident AF were eligible for early rhythm-control.Eligible participants were older (70 years vs 63 years) and more likely to be female (42% vs 21%) compared with ineligible patients. Of 9004 participants with full primary care data, 874 (9.02%) received early rhythm-control. Safety outcomes were not different between patients receiving early rhythm-control and controls. The primary outcome of EAST-AFNET 4, a composite of cardiovascular death, stroke/transient ischaemic attack and hospitalisation for heart failure or acute coronary syndrome occurred less often in participants receiving early rhythm-control compared with controls in the entire cohort (HR 0.82, 95% CI 0.71 to 0.94, p=0.005). In the propensity-score matched analysis, early rhythm-control did not significantly decrease of the primary outcome compared with usual care (HR 0.87, 95% CI 0.72 to 1.04, p=0.124).

Conclusion

Around 80% of participants diagnosed with AF in the UK population are eligible for early rhythm-control. Early rhythm-control therapy was safe in routine care.",,doi:https://doi.org/10.1136/heartjnl-2022-321196; html:https://europepmc.org/articles/PMC9664114; pdf:https://europepmc.org/articles/PMC9664114?pdf=render 34693751,https://doi.org/10.1177/14799731211053332,The diagnosis of asthma. Can physiological tests of small airways function help?,"Almeshari MA, Stockley J, Sapey E.",,Chronic respiratory disease,2021,2021-01-01,Y,Diagnosis; Asthma; Spirometry; Oscillometry; Small Airways Function,,,"Asthma is a common, chronic, and heterogeneous disease with a global impact and substantial economic costs. It is also associated with significant mortality and morbidity and the burden of undiagnosed asthma is significant. Asthma can be difficult to diagnose as there is no gold standard test and, while spirometry is central in diagnosing asthma, it may not be sufficient to confirm or exclude the diagnosis. The most commonly reported spirometric measures (forced expiratory volume in one second (FEV1) and forced vital capacity assess function in the larger airways. However, small airway dysfunction is highly prevalent in asthma and some studies suggest small airway involvement is one of the earliest disease manifestations. Moreover, there are new inhaled therapies with ultrafine particles that are specifically designed to target the small airways. Potentially, tests of small airways may more accurately diagnose early or mild asthma and assess the response to treatment than spirometry. Furthermore, some assessment techniques do not rely on forced ventilatory manoeuvres and may, therefore, be easier for certain groups to perform. This review discusses the current evidence of small airways tests in asthma and future research that may be needed to further assess their utility.",,doi:https://doi.org/10.1177/14799731211053332; html:https://europepmc.org/articles/PMC8543738; pdf:https://europepmc.org/articles/PMC8543738?pdf=render 37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render @@ -670,8 +671,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 37489768,https://doi.org/10.1161/jaha.122.029296,Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.,"Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.",,Journal of the American Heart Association,2023,2023-07-25,Y,Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records,,,"Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.",,doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296 34038519,https://doi.org/10.1093/ageing/afab084,Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,Age and ageing,2021,2021-09-01,Y,Recruitment; Older People; Registry; Sarcopenia,,,"

Background

sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population.

Methods

six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates.

Results

sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies.

Conclusion

recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.",,doi:https://doi.org/10.1093/ageing/afab084; html:https://europepmc.org/articles/PMC8437066; pdf:https://europepmc.org/articles/PMC8437066?pdf=render 34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674 -36208161,https://doi.org/10.1093/eurheartj/ehac426,CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Thomas Lumbers R, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, van Thiel G, van Bochove K, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, CODE-EHR international consensus group.",,European heart journal,2022,2022-10-01,Y,,,,"Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes.",,doi:https://doi.org/10.1093/eurheartj/ehac426; html:https://europepmc.org/articles/PMC9452067; pdf:https://europepmc.org/articles/PMC9452067?pdf=render 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"

Introduction

A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.

Methods

This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.

Results

The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.

Discussion

The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.

Conclusion

It is hoped that this framework will evolve with use and feedback.",,doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render +36208161,https://doi.org/10.1093/eurheartj/ehac426,CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Thomas Lumbers R, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, van Thiel G, van Bochove K, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, CODE-EHR international consensus group.",,European heart journal,2022,2022-10-01,Y,,,,"Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes.",,doi:https://doi.org/10.1093/eurheartj/ehac426; html:https://europepmc.org/articles/PMC9452067; pdf:https://europepmc.org/articles/PMC9452067?pdf=render 34514354,https://doi.org/10.1093/jamiaopen/ooab001,Transforming and evaluating electronic health record disease phenotyping algorithms using the OMOP common data model: a case study in heart failure.,"Papez V, Moinat M, Payralbe S, Asselbergs FW, Lumbers RT, Hemingway H, Dobson R, Denaxas S.",,JAMIA open,2021,2021-02-04,Y,Phenotyping; Heart Failure; Algorithms; Ehr; Omop,,,"

Objective

The aim of the study was to transform a resource of linked electronic health records (EHR) to the OMOP common data model (CDM) and evaluate the process in terms of syntactic and semantic consistency and quality when implementing disease and risk factor phenotyping algorithms.

Materials and methods

Using heart failure (HF) as an exemplar, we represented three national EHR sources (Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care, Office for National Statistics) into the OMOP CDM 5.2. We compared the original and CDM HF patient population by calculating and presenting descriptive statistics of demographics, related comorbidities, and relevant clinical biomarkers.

Results

We identified a cohort of 502 536 patients with the incident and prevalent HF and converted 1 099 195 384 rows of data from 216 581 914 encounters across three EHR sources to the OMOP CDM. The largest percentage (65%) of unmapped events was related to medication prescriptions in primary care. The average coverage of source vocabularies was >98% with the exception of laboratory tests recorded in primary care. The raw and transformed data were similar in terms of demographics and comorbidities with the largest difference observed being 3.78% in the prevalence of chronic obstructive pulmonary disease (COPD).

Conclusion

Our study demonstrated that the OMOP CDM can successfully be applied to convert EHR linked across multiple healthcare settings and represent phenotyping algorithms spanning multiple sources. Similar to previous research, challenges mapping primary care prescriptions and laboratory measurements still persist and require further work. The use of OMOP CDM in national UK EHR is a valuable research tool that can enable large-scale reproducible observational research.",,doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render 35143670,https://doi.org/10.1093/molbev/msac034,The Carbon Footprint of Bioinformatics.,"Grealey J, Lannelongue L, Saw WY, Marten J, Méric G, Ruiz-Carmona S, Inouye M.",,Molecular biology and evolution,2022,2022-03-01,Y,Bioinformatics; Genomics; Carbon Footprint; Green Algorithms,,,"Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.",,doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render; pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf 34266851,https://doi.org/10.1136/bmjhci-2021-100356,Development of a core competency framework for clinical informatics. ,"Davies A, Mueller J, Hassey A, Moulton G.",,BMJ health & care informatics,2021,2021-07-01,Y,,,,"Until this point there was no national core competency framework for clinical informatics in the UK. We report on the final two iterations of work carried out in the formation of a national core competency framework. This follows an initial systematic literature review of existing skills and competencies and a job listing analysis.MethodsAn iterative approach was applied to framework development. Using a mixed-methods design we carried out semi-structured interviews with participants involved in informatics (n=15). The framework was updated based on the interview findings and was subsequently distributed as part of a bespoke online digital survey for wider participation (n=87). The final version of the framework is based on the findings of the survey. Over 102 people reviewed the framework as part of the interview or survey process. This led to a final core competency framework containing 6 primary domains with 36 subdomains containing 111 individual competencies. An iterative mixed-methods approach for competency development involving the target community was appropriate for development of the competency framework. There is some contention around the depth of technical competencies required. Care is also needed to avoid professional burnout, as clinicians and healthcare practitioners already have clinical competencies to maintain. Therefore, how the framework is applied in practice and how practitioners meet the competencies requires careful consideration.",,doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render diff --git a/data/papers.csv b/data/papers.csv index b4fcaf64..80760809 100644 --- a/data/papers.csv +++ b/data/papers.csv @@ -73,10 +73,10 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 36647111,https://doi.org/10.1186/s12911-022-02093-0,"Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration.","Abbasizanjani H, Torabi F, Bedston S, Bolton T, Davies G, Denaxas S, Griffiths R, Herbert L, Hollings S, Keene S, Khunti K, Lowthian E, Lyons J, Mizani MA, Nolan J, Sudlow C, Walker V, Whiteley W, Wood A, Akbari A, CVD-COVID-UK/COVID-IMPACT Consortium.",,BMC medical informatics and decision making,2023,2023-01-16,Y,Population Health; Electronic Health Record; Reproducible Research; Common Data Model; Data Harmonisation; Sail Databank; Covid-19; Trusted Research Environments; Nhs Digital Tre For England,,,"

Background

The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt.

Methods

Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer.

Results

Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information.

Conclusions

We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.",,doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?pdf=render 35796183,https://doi.org/10.1177/01410768221107119,"SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.","Hollinghurst J, North L, Szakmany T, Pugh R, Davies GA, Sivakumaran S, Jarvis R, Rolles M, Pickrell WO, Akbari A, Davies G, Griffiths R, Lyons J, Torabi F, Fry R, Gravenor MB, Lyons RA.",,Journal of the Royal Society of Medicine,2022,2022-07-07,Y,Public Health; Healthcare Workers; Infection Risk; Covid-19; Sars-cov-2,,,"

Objectives

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

Design

Observational, longitudinal, national cohort study.

Setting

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

Participants

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

Main outcome measures

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

Results

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

Conclusions

These findings have important policy implications for the prioritisation of vaccination, testing, training and personal protective equipment provision for patient-facing roles and the higher risk staff groups.",,doi:https://doi.org/10.1177/01410768221107119; html:https://europepmc.org/articles/PMC9747896; pdf:https://europepmc.org/articles/PMC9747896?pdf=render 36332519,https://doi.org/10.1016/j.ijmedinf.2022.104905,Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.,"Davies A, Hassey A, Williams J, Moulton G.",,International journal of medical informatics,2022,2022-10-30,N,Informatics; Core Competencies; Competency Framework; Healthcare Workforce; Informaticians,,,"

Background

The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles.

Methods

The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance.

Results

A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework.

Conclusion

Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).",,doi:https://doi.org/10.1016/j.ijmedinf.2022.104905 -37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render 34706900,https://doi.org/10.1136/emermed-2021-211706,Comparative analysis of major incident triage tools in children: a UK population-based analysis.,"Vassallo J, Chernbumroong S, Malik N, Xu Y, Keene D, Gkoutos G, Lyttle MD, Smith J, in collaboration with PERUKI (Paediatric Emergency Research in the UK and Ireland).",,Emergency medicine journal : EMJ,2021,2021-10-27,Y,Planning; Paediatrics; Major Incident; Clinical Care; Triage; Major Incidents,,,"

Introduction

Triage is a key principle in the effective management of major incidents. There is currently a paucity of evidence to guide the triage of children. The aim of this study was to perform a comparative analysis of nine adult and paediatric triage tools, including the novel 'Sheffield Paediatric Triage Tool' (SPTT), assessing their ability in identifying patients needing life-saving interventions (LSIs).

Methods

A 10-year (2008-2017) retrospective database review of the Trauma Audit Research Network (TARN) Database for paediatric patients (<16 years) was performed. Primary outcome was identification of patients receiving one or more LSIs from a previously defined list. Secondary outcomes included mortality and prediction of Injury Severity Score (ISS) >15. Primary analysis was conducted on patients with complete prehospital physiological data with planned secondary analyses using first recorded data. Performance characteristics were evaluated using sensitivity, specificity, undertriage and overtriage.

Results

15 133 patients met TARN inclusion criteria. 4962 (32.8%) had complete prehospital physiological data and 8255 (54.5%) had complete first recorded physiological data. The majority of patients were male (69.5%), with a median age of 11.9 years. The overwhelming majority of patients (95.4%) sustained blunt trauma, yielding a median ISS of 9 and overall, 875 patients (17.6%) received at least one LSI. The SPTT demonstrated the greatest sensitivity of all triage tools at identifying need for LSI (92.2%) but was associated with the highest rate of overtriage (75.0%). Both the Paediatric Triage Tape (sensitivity 34.1%) and JumpSTART (sensitivity 45.0%) performed less well at identifying LSI. By contrast, the adult Modified Physiological Triage Tool-24 (MPTT-24) triage tool had the second highest sensitivity (80.8%) with tolerable rates of overtriage (70.2%).

Conclusion

The SPTT and MPTT-24 outperform existing paediatric triage tools at identifying those patients requiring LSIs. This may necessitate a change in recommended practice. Further work is needed to determine the optimum method of paediatric major incident triage, but consideration should be given to simplifying major incident triage by the use of one generic tool (the MPTT-24) for adults and children.",,doi:https://doi.org/10.1136/emermed-2021-211706; html:https://europepmc.org/articles/PMC9510399; pdf:https://europepmc.org/articles/PMC9510399?pdf=render 35273122,https://doi.org/10.1136/heartjnl-2021-320325,Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort.,"Handy A, Banerjee A, Wood AM, Dale C, Sudlow CLM, Tomlinson C, Bean D, Thygesen JH, Mizani MA, Katsoulis M, Takhar R, Hollings S, Denaxas S, Walker V, Dobson R, Sofat R, CVD-COVID-UK Consortium.",,Heart (British Cardiac Society),2022,2022-05-25,Y,Atrial fibrillation; epidemiology; Electronic Health Records; drug monitoring; Covid-19,,,"

Objective

To evaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and at high risk of stroke (CHA2DS2-VASc score ≥2) and investigate whether pre-existing AT use may improve COVID-19 outcomes.

Methods

Individuals with AF and CHA2DS2-VASc score ≥2 on 1 January 2020 were identified using electronic health records for 56 million people in England and were followed up until 1 May 2021. Factors associated with pre-existing AT use were analysed using logistic regression. Differences in COVID-19-related hospitalisation and death were analysed using logistic and Cox regression in individuals with pre-existing AT use versus no AT use, anticoagulants (AC) versus antiplatelets (AP), and direct oral anticoagulants (DOACs) versus warfarin.

Results

From 972 971 individuals with AF (age 79 (±9.3), female 46.2%) and CHA2DS2-VASc score ≥2, 88.0% (n=856 336) had pre-existing AT use, 3.8% (n=37 418) had a COVID-19 hospitalisation and 2.2% (n=21 116) died, followed up to 1 May 2021. Factors associated with no AT use included comorbidities that may contraindicate AT use (liver disease and history of falls) and demographics (socioeconomic status and ethnicity). Pre-existing AT use was associated with lower odds of death (OR=0.92, 95% CI 0.87 to 0.96), but higher odds of hospitalisation (OR=1.20, 95% CI 1.15 to 1.26). AC versus AP was associated with lower odds of death (OR=0.93, 95% CI 0.87 to 0.98) and higher hospitalisation (OR=1.17, 95% CI 1.11 to 1.24). For DOACs versus warfarin, lower odds were observed for hospitalisation (OR=0.86, 95% CI 0.82 to 0.89) but not for death (OR=1.00, 95% CI 0.95 to 1.05).

Conclusions

Pre-existing AT use may be associated with lower odds of COVID-19 death and, while not evidence of causality, provides further incentive to improve AT coverage for eligible individuals with AF.",,doi:https://doi.org/10.1136/heartjnl-2021-320325; html:https://europepmc.org/articles/PMC8931797; pdf:https://europepmc.org/articles/PMC8931797?pdf=render 35706489,https://doi.org/10.1016/j.eclinm.2022.101428,Impact of ethnicity on the accuracy of measurements of oxygen saturations: A retrospective observational cohort study.,"Bangash MN, Hodson J, Evison F, Patel JM, Johnston AM, Gallier S, Sapey E, Parekh D.",,EClinicalMedicine,2022,2022-05-06,Y,Inequalities; Ethnicity; Oxygen Saturations,,,"

Background

Pulse oximeters are routinely used in community and hospital settings worldwide as a rapid, non-invasive, and readily available bedside tool to approximate blood oxygenation. Potential racial biases in peripheral oxygen saturation (SpO2) measurements may influence the accuracy of pulse oximetry readings and impact clinical decision making. We aimed to assess whether the accuracy of oxygen saturation measured by SpO2, relative to arterial blood gas (SaO2), varies by ethnicity.

Methods

In this large retrospective observational cohort study covering four NHS Hospitals serving a large urban population in Birmingham, United Kingdom, consecutive pairs of SpO2 and SaO2 measurements taken on the same patient within an interval of less than 20 min were identified from electronic patient records. Where multiple pairs of measurements were recorded in a spell, only the first was included in the analysis. The differences between SpO2 and SaO2 measurements were compared across groups of self-identified ethnicity. These differences were subsequently adjusted for age, sex, bilirubin, systolic blood pressure, carboxyhaemaglobin saturations and the time interval between SpO2 and SaO2 measurements.

Findings

Paired O2 saturation measurements from 16,818 inpatient spells between 1st January 2017 and 18th February 2021 were analysed. The cohort self-identified as being of White (81.2%), Asian (11.7%), Black (4.0%), or Other (3.2%) ethnicities. Across the cohort, SpO2 was statistically significantly higher than SaO2 (p < 0.0001), with medians of 98% (interquartile range [IQR]: 95-100%) vs. 97% (IQR: 96-99%), and a median difference of 0.5% points (pps; 95% confidence interval [CI]: 0.5-0.6). However, the size of this difference varied considerably with the magnitude of SaO2, with SpO2 overestimating by a median by 3.8pp (IQR: 0.4, 8.8) for SaO2 values <90% but underestimating by a median of 0.4pp (IQR: -2.0, 1.4) for an SaO2 of 95%. The differences between SpO2 and SaO2 were also found to vary by ethnicity, with this difference being 0.8pp (95% CI: 0.6-1.0, p < 0.0001) greater in those of Black vs. White ethnicity. These differences resulted in 8.7% vs. 6.1% of Black vs. White patients who were classified as normoxic on SpO2 actually being hypoxic on the gold standard SaO2 (odds ratio: 1.47, 95% CI: 1.09-1.98, p = 0.012).

Interpretation

Pulse oximetry may overestimate O2 saturation, and this is possibly more pronounced in patients of Black ethnicity. Prospective studies are urgently warranted to assess the impact of ethnicity on the accuracy of pulse oximetry, to ensure care is optimised for all.

Funding

PIONEER, the Health Data Research UK (HDR-UK) Health Data Research Hub in acute care.",,doi:https://doi.org/10.1016/j.eclinm.2022.101428; html:https://europepmc.org/articles/PMC9096912; pdf:https://europepmc.org/articles/PMC9096912?pdf=render +37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render 36526323,https://doi.org/10.1136/bmjopen-2022-068252,"Identification of risk factors associated with prolonged hospital stay following primary knee replacement surgery: a retrospective, longitudinal observational study.","Wilson R, Margelyte R, Redaniel MT, Eyles E, Jones T, Penfold C, Blom A, Elliott A, Harper A, Keen T, Pitt M, Judge A.",,BMJ open,2022,2022-12-16,Y,Knee; Rheumatology; Statistics & Research Methods; Orthopaedic & Trauma Surgery; Adult Orthopaedics,,,"

Objectives

To identify risk factors associated with prolonged length of hospital stay and staying in hospital longer than medically necessary following primary knee replacement surgery.

Design

Retrospective, longitudinal observational study.

Setting

Elective knee replacement surgeries between 2016 and 2019 were identified using routinely collected data from an NHS Trust in England.

Participants

There were 2295 knee replacement patients with complete data included in analysis. The mean age was 68 (SD 11) and 60% were female.

Outcome measures

We assessed a binary length of stay outcome (>7 days), a continuous length of stay outcome (≤30 days) and a binary measure of whether patients remained in hospital when they were medically fit for discharge.

Results

The mean length of stay was 5.0 days (SD 3.9), 15.4% of patients were in hospital for >7 days and 7.1% remained in hospital when they were medically fit for discharge. Longer length of stay was associated with older age (b=0.08, 95% CI 0.07 to 0.09), female sex (b=0.36, 95% CI 0.06 to 0.67), high deprivation (b=0.98, 95% CI 0.47 to 1.48) and more comorbidities (b=2.48, 95% CI 0.15 to 4.81). Remaining in hospital beyond being medically fit for discharge was associated with older age (OR=1.07, 95% CI 1.05 to 1.09), female sex (OR=1.71, 95% CI 1.19 to 2.47) and high deprivation (OR=2.27, 95% CI 1.27 to 4.06).

Conclusions

The regression models could be used to identify which patients are likely to occupy hospital beds for longer. This could be helpful in scheduling operations to aid hospital efficiency by planning these patients' operations for when the hospital is less busy.",,doi:https://doi.org/10.1136/bmjopen-2022-068252; html:https://europepmc.org/articles/PMC9764602; pdf:https://europepmc.org/articles/PMC9764602?pdf=render 35468332,https://doi.org/10.1016/s1473-3099(22)00141-4,Severity of omicron variant of concern and effectiveness of vaccine boosters against symptomatic disease in Scotland (EAVE II): a national cohort study with nested test-negative design.,"Sheikh A, Kerr S, Woolhouse M, McMenamin J, Robertson C, EAVE II Collaborators.",,The Lancet. Infectious diseases,2022,2022-04-22,Y,,,,"

Background

Since its emergence in November, 2021, in southern Africa, the SARS-CoV-2 omicron variant of concern (VOC) has rapidly spread across the world. We aimed to investigate the severity of omicron and the extent to which booster vaccines are effective in preventing symptomatic infection.

Methods

In this study, using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, we did a cohort analysis with a nested test-negative design incident case-control study covering the period Nov 1-Dec 19, 2021, to provide initial estimates of omicron severity and the effectiveness of vaccine boosters against symptomatic disease relative to 25 weeks or more after the second vaccine dose. Primary care data derived from 940 general practices across Scotland were linked to laboratory data and hospital admission data. We compared outcomes between infection with the delta VOC (defined as S-gene positive) and the omicron VOC (defined as S-gene negative). We assessed effectiveness against symptomatic SARS-CoV-2 infection, with infection confirmed through a positive RT-PCR.

Findings

By Dec 19, 2021, there were 23 840 S-gene-negative cases in Scotland, which were predominantly among those aged 20-39 years (11 732 [49·2%]). The proportion of S-gene-negative cases that were possible reinfections was more than ten times that of S-gene-positive cases (7·6% vs 0·7%; p<0·0001). There were 15 hospital admissions in S-gene-negative individuals, giving an adjusted observed-to-expected admissions ratio of 0·32 (95% CI 0·19-0·52). The booster vaccine dose was associated with a 57% (54-60) reduction in the risk of symptomatic S-gene-negative infection relative to individuals who tested positive 25 weeks or more after the second vaccine dose.

Interpretation

These early national data suggest that omicron is associated with a two-thirds reduction in the risk of COVID-19 hospitalisation compared with delta. Although offering the greatest protection against delta, the booster dose of vaccination offers substantial additional protection against the risk of symptomatic COVID-19 for omicron compared with 25 weeks or more after the second vaccine dose.

Funding

Health Data Research UK, National Core Studies, Public Health Scotland, Scottish Government, UK Research and Innovation, and University of Edinburgh.",,doi:https://doi.org/10.1016/S1473-3099(22)00141-4; html:https://europepmc.org/articles/PMC9033213 37368589,https://doi.org/10.3390/toxics11060489,Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.,"Kuo CL, Liu R, Godoy LDC, Pilling LC, Fortinsky RH, Brugge D.",,Toxics,2023,2023-05-28,Y,Pm10; Pm2.5; No2; Nox; Pm2.5 Absorbance; Pm2.5–10,,,"Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.",,doi:https://doi.org/10.3390/toxics11060489; html:https://europepmc.org/articles/PMC10301073; pdf:https://europepmc.org/articles/PMC10301073?pdf=render @@ -91,8 +91,8 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 37022988,https://doi.org/10.1371/journal.pmed.1004191,"Infant feeding method and special educational need in 191,745 Scottish schoolchildren: A national, population cohort study.","Adams LJ, Pell JP, Mackay DF, Clark D, King A, Fleming M.",,PLoS medicine,2023,2023-04-06,Y,,,,"

Background

While special educational needs (SEN) are increasingly recorded among schoolchildren, infant breastfeeding has been associated with reduced incidence of childhood physical and mental health problems. This study investigated relationships between infant feeding method and risk of all-cause and cause-specific SEN.

Methods and findings

A population cohort of schoolchildren in Scotland was constructed by linking together health (maternity, birth, and health visitor records) and education (annual school pupil census) databases. Inclusion was restricted to singleton children, born in Scotland from 2004 onwards with available breastfeeding data and who attended local authority mainstream or special schools between 2009 and 2013. Generalised estimating equation models with a binomial distribution and logit link function investigated associations between infant feeding method at 6 to 8 weeks and all-cause and cause-specific SEN, adjusting for sociodemographic and maternity factors. Of 191,745 children meeting inclusion criteria, 126,907 (66.2%) were formula-fed, 48,473 (25.3%) exclusively breastfed, and 16,365 (8.5%) mixed-fed. Overall, 23,141 (12.1%) children required SEN. Compared with formula feeding, mixed feeding and exclusive breastfeeding, respectively, were associated with decreased all-cause SEN (OR 0.90, 95% CI [0.84,0.95], p < 0.001 and 0.78, [0.75,0.82], p < 0.001), and SEN attributed to learning disabilities (0.75, [0.65,0.87], p < 0.001 and 0.66, [0.59,0.74], p < 0.001), and learning difficulties (0.85, [0.77,0.94], p = 0.001 and 0.75, [0.70,0.81], p < 0.001). Compared with formula feeding, exclusively breastfed children had less communication problems (0.81, [0.74,0.88], p = 0.001), social-emotional-behavioural difficulties (0.77, [0.70,0.84], p = 0.001), sensory impairments (0.79, [0.65,0.95], p = 0.01), physical motor disabilities (0.78, [0.66,0.91], p = 0.002), and physical health conditions (0.74, [0.63,0.87], p = 0.01). There were no significant associations for mixed-fed children (communication problems (0.94, [0.83,1.06], p = 0.312), social-emotional-behavioural difficulties (0.96, [0.85,1.09], p = 0.541), sensory impairments (1.07, [0.84,1.37], p = 0.579), physical motor disabilities (0.97, [0.78,1.19], p = 0.754), and physical health conditions (0.93, [0.74,1.16], p = 0.504)). Feeding method was not significantly associated with mental health conditions (exclusive 0.58 [0.33,1.03], p = 0.061 and mixed 0.74 [0.36,1.53], p = 0.421) or autism (exclusive 0.88 [0.77,1.01], p = 0.074 and mixed 1.01 [0.84,1.22], p = 0.903). Our study was limited since only 6- to 8-week feeding method was available precluding differentiation between never-breastfed infants and those who stopped breastfeeding before 6 weeks. Additionally, we had no data on maternal and paternal factors such as education level, IQ, employment status, race/ethnicity, or mental and physical health.

Conclusions

In this study, we observed that both breastfeeding and mixed feeding at 6 to 8 weeks were associated with lower risk of all-cause SEN, and SEN attributed to learning disabilities and learning difficulty. Many women struggle to exclusively breastfeed for the full 6 months recommended by WHO; however, this study provides evidence that a shorter duration of nonexclusive breastfeeding could nonetheless be beneficial with regard to the development of SEN. Our findings augment the existing evidence base concerning the advantages of breastfeeding and reinforce the importance of breastfeeding education and support.",,doi:https://doi.org/10.1371/journal.pmed.1004191; html:https://europepmc.org/articles/PMC10079126; pdf:https://europepmc.org/articles/PMC10079126?pdf=render 33252680,https://doi.org/10.1093/ageing/afaa252,A comparison of two national frailty scoring systems. ,"Hollinghurst J, Housley G, Watkins A, Clegg A, Gilbert T, Conroy SP.",,Age and ageing,2021,2021-06-01,N,,,,"The electronic Frailty Index (eFI) has been developed in primary care settings. The Hospital Frailty Risk Score (HFRS) was derived using secondary care data. Compare the two different tools for identifying frailty in older people admitted to hospital. Retrospective cohort study using the Secure Anonymised Information Linkage Databank, comprising 126,600 people aged 65+ who were admitted as an emergency to hospital in Wales from January 2013 up until December 2017. Pearson's correlation coefficient and weighted kappa were used to assess the correlation between the tools. Cox and logistic regression were used to estimate hazard ratios (HRs) and odds ratios (ORs). The Concordance statistic and area under the receiver operating curves (AUROC) were estimated to determine discrimination. Pearson's correlation coefficient was 0.26 and the weighted kappa was 0.23. Comparing the highest to the least frail categories in the two scores the HRs for 90-day mortality, 90-day emergency readmission and care home admissions within 1-year using the HFRS were 1.41, 1.69 and 4.15 for the eFI 1.16, 1.63 and 1.47. Similarly, the ORs for inpatient death, length of stay greater than 10 days and readmission within 30-days were 1.44, 2.07 and 1.52 for the HFRS, and 1.21, 1.21 and 1.44 for the eFI. AUROC was determined as having no clinically relevant difference between the tools. The eFI and HFRS have a low correlation between their scores. The HRs and ORs were higher for the increasing frailty categories for both the HFRS and eFI.",,doi:https://doi.org/10.1093/ageing/afaa252; html:https://europepmc.org/articles/PMC8244560; pdf:https://europepmc.org/articles/PMC8244560?pdf=render; doi:https://doi.org/10.1093/ageing/afaa252 33045103,https://doi.org/10.1002/gps.5446,Socio-economic predictors of time to care home admission in people living with dementia in Wales: A routine data linkage study. ,"Giebel C, Hollinghurst J, Akbari A, Schnier C, Wilkinson T, North L, Gabbay M, Rodgers S.",,International journal of geriatric psychiatry,2021,2020-10-19,Y,,,,"Limited research has shown that people with dementia (PwD) from lower socio-economic backgrounds can face difficulties in accessing the right care at the right time. This study examined whether socio-economic status (SES) and rural versus urban living location are associated with the time between diagnosis and care home admission in PwD living in Wales, UK. This study linked routine health data and an e-cohort of PwD who have been admitted into a care home between 2000 and 2018 living in Wales. Survival analysis explored the effects of SES, living location, living situation, and frailty on the time between diagnosis and care home admission. In 34,514 PwD, the average time between diagnosis and care home admission was 1.5 (±1.4) years. Cox regression analysis showed that increased age, living alone, frailty, and living in less disadvantaged neighbourhoods were associated with faster rate to care home admission. Living in rural regions predicted a slower rate until care home admission. This is one of the first studies to show a link between socio-economic factors on time to care home admission in dementia. Future research needs to address variations in care needs between PwD from different socio-economic and geographical backgrounds.",,doi:https://doi.org/10.1002/gps.5446; html:https://europepmc.org/articles/PMC7984448; pdf:https://europepmc.org/articles/PMC7984448?pdf=render -34487522,https://doi.org/10.1093/cid/ciab754,Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.,"Grint DJ, Wing K, Houlihan C, Gibbs HP, Evans SJW, Williamson E, McDonald HI, Bhaskaran K, Evans D, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AYS, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Smeeth L, Goldacre B, Eggo RM.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2022,2022-08-01,Y,Alpha; Hospital Admission; Case Fatality; Sars-cov-2,,,"

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death.

Methods

With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021.

Results

Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P = .45).

Conclusions

The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.",,doi:https://doi.org/10.1093/cid/ciab754; html:https://europepmc.org/articles/PMC8522415; pdf:https://europepmc.org/articles/PMC8522415?pdf=render 34544601,https://doi.org/10.1016/j.vaccine.2021.09.019,"Inequalities in coverage of COVID-19 vaccination: A population register based cross-sectional study in Wales, UK.","Perry M, Akbari A, Cottrell S, Gravenor MB, Roberts R, Lyons RA, Bedston S, Torabi F, Griffiths L.",,Vaccine,2021,2021-09-08,Y,Ethnic Groups; Vaccination; Socioeconomic Factors; Immunisation; Covid-19 Vaccines,,,"The COVID-19 pandemic has highlighted existing health inequalities for ethnic minority groups and those living in more socioeconomically deprived areas in the UK. With higher levels of severe outcomes in these groups, equitable vaccination coverage should be prioritised. The aim of this study was to identify inequalities in coverage of COVID-19 vaccination in Wales, UK and to highlight areas which may benefit from routine enhanced surveillance and targeted interventions. Records within the Wales Immunisation System (WIS) population register were linked to the Welsh Demographic Service Dataset (WDSD) and central list of shielding patients, held within the Secure Anonymised Information Linkage (SAIL) Databank. Ethnic group was derived from the 2011 census and over 20 administrative electronic health record (EHR) data sources. Uptake of first dose of any COVID-19 vaccine was analysed over time, with the odds of being vaccinated as at 25th April 2021 by sex, health board of residence, rural/urban classification, deprivation quintile and ethnic group presented. Using logistic regression models, analyses were adjusted for age group, care home resident status, health and social care worker status and shielding status. This study included 1,256,412 individuals aged 50 years and over. Vaccine coverage increased steadily from 8th December 2020 until mid-April 2021. Overall uptake of first dose of COVID-19 vaccine in this group was 92.1%. After adjustment the odds of being vaccinated were lower for individuals who were male, resident in the most deprived areas, resident in an urban area and an ethnic group other than White. The largest inequality was seen between ethnic groups, with the odds of being vaccinated 0.22 (95 %CI 0.21-0.24) if in any Black ethnic group compared to any White ethnic group. Ongoing monitoring of inequity in uptake of vaccinations is required, with better targeted interventions and engagement with deprived and ethnic communities to improve vaccination uptake.",,doi:https://doi.org/10.1016/j.vaccine.2021.09.019; html:https://europepmc.org/articles/PMC8423991 +34487522,https://doi.org/10.1093/cid/ciab754,Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.,"Grint DJ, Wing K, Houlihan C, Gibbs HP, Evans SJW, Williamson E, McDonald HI, Bhaskaran K, Evans D, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AYS, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Smeeth L, Goldacre B, Eggo RM.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2022,2022-08-01,Y,Alpha; Hospital Admission; Case Fatality; Sars-cov-2,,,"

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death.

Methods

With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021.

Results

Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P = .45).

Conclusions

The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.",,doi:https://doi.org/10.1093/cid/ciab754; html:https://europepmc.org/articles/PMC8522415; pdf:https://europepmc.org/articles/PMC8522415?pdf=render 34148733,https://doi.org/10.1016/j.bja.2021.05.018,Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.,"Abbott TEF, Fowler AJ, Dobbs TD, Gibson J, Shahid T, Dias P, Akbari A, Whitaker IS, Pearse RM.",,British journal of anaesthesia,2021,2021-06-11,Y,Surgery; Anaesthesia; epidemiology; Public Policy; Covid-19,,,"

Background

The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery.

Methods

Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI).

Results

We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001).

Conclusions

The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.",,doi:https://doi.org/10.1016/j.bja.2021.05.018; html:https://europepmc.org/articles/PMC8192173; pdf:https://europepmc.org/articles/PMC8192173?pdf=render 37088955,https://doi.org/10.1177/02692163231167212,"Deaths at home, area-based deprivation and the effect of the Covid-19 pandemic: An analysis of mortality data across four nations.","Leniz J, Davies JM, Bone AE, Hocaoglu M, Verne J, Barclay S, Murtagh FEM, Fraser LK, Higginson IJ, Sleeman KE.",,Palliative medicine,2023,2023-04-23,Y,Mortality; Palliative care; Terminal Care; Inequalities; Place Of Death; Deprivation; Pandemics; Socio-economic Position; Covid-19,,,"

Background

The number and proportion of home deaths in the UK increased during the Covid-19 pandemic. It is not known whether these changes were experienced disproportionately by people from different socioeconomic groups.

Aim

To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.

Design

Retrospective cohort study using population-based individual-level mortality data.

Setting/participants

All registered deaths in England, Wales, Scotland and Northern Ireland. The proportion of home deaths between 28th March and 31st December 2020 was compared with the same period in 2019. We used Poisson regression models to evaluate the association between decedent's area-based level of deprivation and risk of home death, as well as the interaction between deprivation and year of death, for each nation separately.

Results

Between the 28th March and 31st December 2020, 409,718 deaths were recorded in England, 46,372 in Scotland, 26,410 in Wales and 13,404 in Northern Ireland. All four nations showed an increase in the adjusted proportion of home deaths between 2019 and 2020, ranging from 21 to 28%. This increase was lowest for people living in the most deprived areas in all nations, with evidence of a deprivation gradient in England.

Conclusions

The Covid-19 pandemic exacerbated a previously described socioeconomic inequality in place of death in the UK. Further research to understand the reasons for this change and if this inequality has been sustained is needed.",,doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882 35915784,https://doi.org/10.1016/j.lanepe.2022.100462,Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys.,"Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters CE, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,The Lancet regional health. Europe,2022,2022-07-28,Y,"Rt-pcr, Reverse Transcription Polymerase Chain Reaction; Ct, Cycle Threshold; Covid-19; Sars-cov-2; Nhs, National Health Service; B-spline, Basis Spline; Rim, Random Iterative Method; Ltla, Lower-tier Local Authority; P-spline, Penalised Spline; Ukhsa, Uk Health Security Agency; Omicron Variant; Ba.2 Sublineage; Random Community Surveys",,,"

Background

The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.

Methods

In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).

Findings

We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0-0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4-67.2) were BA.1; N=568, 35.2% (32.8-37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34-0.41). The highest proportion of BA.2 among positives was found in London.

Interpretation

In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.

Funding

Department of Health and Social Care, England.",,doi:https://doi.org/10.1016/j.lanepe.2022.100462; html:https://europepmc.org/articles/PMC9330654; pdf:https://europepmc.org/articles/PMC9330654?pdf=render @@ -115,6 +115,7 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 35798890,https://doi.org/10.1038/s41564-022-01143-7,SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway.,"Willett BJ, Grove J, MacLean OA, Wilkie C, De Lorenzo G, Furnon W, Cantoni D, Scott S, Logan N, Ashraf S, Manali M, Szemiel A, Cowton V, Vink E, Harvey WT, Davis C, Asamaphan P, Smollett K, Tong L, Orton R, Hughes J, Holland P, Silva V, Pascall DJ, Puxty K, da Silva Filipe A, Yebra G, Shaaban S, Holden MTG, Pinto RM, Gunson R, Templeton K, Murcia PR, Patel AH, Klenerman P, Dunachie S, PITCH Consortium, COVID-19 Genomics UK (COG-UK) Consortium, Haughney J, Robertson DL, Palmarini M, Ray S, Thomson EC.",,Nature microbiology,2022,2022-07-07,Y,,,,"Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.",,doi:https://doi.org/10.1038/s41564-022-01143-7; html:https://europepmc.org/articles/PMC9352574; pdf:https://europepmc.org/articles/PMC9352574?pdf=render 37468507,https://doi.org/10.1038/s41598-023-37580-5,Biobank-scale methods and projections for sparse polygenic prediction from machine learning.,"Raben TG, Lello L, Widen E, Hsu SDH.",,Scientific reports,2023,2023-07-19,Y,,,,"In this paper we characterize the performance of linear models trained via widely-used sparse machine learning algorithms. We build polygenic scores and examine performance as a function of training set size, genetic ancestral background, and training method. We show that predictor performance is most strongly dependent on size of training data, with smaller gains from algorithmic improvements. We find that LASSO generally performs as well as the best methods, judged by a variety of metrics. We also investigate performance characteristics of predictors trained on one genetic ancestry group when applied to another. Using LASSO, we develop a novel method for projecting AUC and correlation as a function of data size (i.e., for new biobanks) and characterize the asymptotic limit of performance. Additionally, for LASSO (compressed sensing) we show that performance metrics and predictor sparsity are in agreement with theoretical predictions from the Donoho-Tanner phase transition. Specifically, a future predictor trained in the Taiwan Precision Medicine Initiative for asthma can achieve an AUC of [Formula: see text] and for height a correlation of [Formula: see text] for a Taiwanese population. This is above the measured values of [Formula: see text] and [Formula: see text], respectively, for UK Biobank trained predictors applied to a European population.",,doi:https://doi.org/10.1038/s41598-023-37580-5; html:https://europepmc.org/articles/PMC10356957; pdf:https://europepmc.org/articles/PMC10356957?pdf=render 32951042,https://doi.org/10.1093/ageing/afaa207,"The impact of COVID-19 on adjusted mortality risk in care homes for older adults in Wales, UK: a retrospective population-based cohort study for mortality in 2016-2020. ","Hollinghurst J, Lyons J, Fry R, Akbari A, Gravenor M, Watkins A, Verity F, Lyons RA.",,Age and ageing,2021,2021-01-01,Y,,,,"mortality in care homes has had a prominent focus during the COVID-19 outbreak. Care homes are particularly vulnerable to the spread of infectious diseases, which may lead to increased mortality risk. Multiple and interconnected challenges face the care home sector in the prevention and management of outbreaks of COVID-19, including adequate supply of personal protective equipment, staff shortages and insufficient or lack of timely COVID-19 testing. to analyse the mortality of older care home residents in Wales during COVID-19 lockdown and compare this across the population of Wales and the previous 4 years. we used anonymised electronic health records and administrative data from the secure anonymised information linkage databank to create a cross-sectional cohort study. We anonymously linked data for Welsh residents to mortality data up to the 14th June 2020. we calculated survival curves and adjusted Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of mortality. We adjusted HRs for age, gender, social economic status and prior health conditions. survival curves show an increased proportion of deaths between 23rd March and 14th June 2020 in care homes for older people, with an adjusted HR of 1.72 (1.55, 1.90) compared with 2016. Compared with the general population in 2016-2019, adjusted care home mortality HRs for older adults rose from 2.15 (2.11, 2.20) in 2016-2019 to 2.94 (2.81, 3.08) in 2020. the survival curves and increased HRs show a significantly increased risk of death in the 2020 study periods.",,doi:https://doi.org/10.1093/ageing/afaa207; html:https://europepmc.org/articles/PMC7546151; pdf:https://europepmc.org/articles/PMC7546151?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/50/1/25/42362959/afaa207.pdf +36807005,https://doi.org/10.1055/a-2038-0541,Long-term outcomes of pouch surveillance and risk of neoplasia in familial adenomatous polyposis.,"Patel RV, Curtius K, Man R, Fletcher J, Cuthill V, Clark SK, von Roon AC, Latchford A.",,Endoscopy,2023,2023-02-17,Y,,,,"

Background

 Long-term pouch surveillance outcomes for familial adenomatous polyposis (FAP) are unknown. We aimed to quantify surveillance outcomes and to determine which of selected possible predictive factors are associated with pouch dysplasia.

Methods

 Retrospective analysis of collected data on 249 patients was performed, analyzing potential risk factors for the development of adenomas or advanced lesions ( ≥ 10 mm/high grade dysplasia (HGD)/cancer) in the pouch body and cuff using Cox proportional hazards models. Kaplan-Meier analyses included landmark time-point analyses at 10 years after surgery to predict the future risk of advanced lesions.

Results

 Of 249 patients, 76 % developed at least one pouch body adenoma, with 16 % developing an advanced pouch body lesion; 18 % developed an advanced cuff lesion. Kaplan-Meier analysis showed a 10-year lag before most advanced lesions developed; cumulative incidence of 2.8 % and 6.4 % at 10 years in the pouch body and cuff, respectively. Landmark analysis suggested the presence of adenomas prior to the 10-year point was associated with subsequent development of advanced lesions in the pouch body (hazard ratio [HR] 4.8, 95 %CI 1.6-14.1; P = 0.004) and cuff (HR 6.8, 95 %CI 2.5-18.3; P < 0.001). There were two HGD and four cancer cases in the cuff and one pouch body cancer; all cases of cancer/HGD that had prior surveillance were preceded by ≥ 10-mm adenomas.

Conclusions

 Pouch adenoma progression is slow and most advanced lesions occur after 10 years. HGD and cancer were rare events. Pouch phenotype in the first decade is associated with the future risk of developing advanced lesions and may guide personalized surveillance beyond 10 years.",,doi:https://doi.org/10.1055/a-2038-0541; html:https://europepmc.org/articles/PMC10465241; pdf:https://europepmc.org/articles/PMC10465241?pdf=render; pdf:http://www.thieme-connect.de/products/ejournals/pdf/10.1055/a-2038-0541.pdf 37254630,https://doi.org/10.1111/acel.13808,"Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.","Liu R, Xiang M, Pilling LC, Melzer D, Wang L, Manning KJ, Steffens DC, Bowden J, Fortinsky RH, Kuchel GA, Rhee TG, Diniz BS, Kuo CL.",,Aging cell,2023,2023-05-30,Y,Cognition; Alzheimer's disease; Vascular dementia; Brain Magnetic Resonance Imaging; Hallmarks Of Biological Aging,,,"Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10-7 ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.",,doi:https://doi.org/10.1111/acel.13808; html:https://europepmc.org/articles/PMC10352557; pdf:https://europepmc.org/articles/PMC10352557?pdf=render; doi:https://doi.org/10.1111/acel.13808 35135770,https://doi.org/10.1136/bmjopen-2021-054027,Evaluation of NEWS2 response thresholds in a retrospective observational study from a UK acute hospital.,"Pankhurst T, Sapey E, Gyves H, Evison F, Gallier S, Gkoutos G, Ball S.",,BMJ open,2022,2022-02-08,Y,Internal Medicine; Health Policy; Health Informatics,,,"

Objective

Use of National Early Warning Score 2 (NEWS2) has been mandated in adults admitted to acute hospitals in England. Urgent clinical review is recommended at NEWS2 ≥5. This policy is recognised as requiring ongoing evaluation. We assessed NEWS2 acquisition, alerting at key thresholds and patient outcomes, to understand how response recommendations would affect clinical resource allocation.

Setting

Adult acute hospital in England.

Design

Retrospective observational cohort study.

Participants

100 362 consecutive admissions between November 2018 and July 2019.

Outcome

Death or admission to intensive care unit within 24 hours of a score.

Methods

NEWS2 were assembled as single scores from consecutive 24-hour time frames, (the first NEWS2 termed 'Index-NEWS2'), or as all scores from the admission (termed All-NEWS2). Scores were excluded when a patient was in intensive care, in the presence of a decision not to attempt cardiopulmonary resuscitation, or on day 1 of elective admission.

Results

A mean of 4.5 NEWS2 were acquired per patient per day. The outcome rate following an Index-NEWS2 was 0.22/100 patient-days. The sensitivity of outcome prediction at Index-NEWS2 ≥5=0.46, and number needed to evaluate (NNE)=52. At this threshold, a mean of 37.6 alerts/100 patient-days would be generated, occurring in 12.3% of patients on any single day. Threshold changes to increase sensitivity by 0.1, would result in a twofold increase in alert rate and 1.5-fold increase in NNE. Overall, NEWS2 classification performance was significantly worse on Index-scores than All-scores (c-statistic=0.78 vs 0.85; p<0.001).

Conclusions

The combination of low event-rate, high alert-rate and low sensitivity, in patients for cardiopulmonary resuscitation, means that at current NEWS2 thresholds, resource demand would be sufficient to meaningfully compete with other pathways to clinical evaluation. In analyses that epitomise in-patient screening, NEWS2 performance suggests a need for re-evaluation of current response recommendations in this population.",,doi:https://doi.org/10.1136/bmjopen-2021-054027; html:https://europepmc.org/articles/PMC8830252; pdf:https://europepmc.org/articles/PMC8830252?pdf=render 36891499,https://doi.org/10.1016/j.ssmph.2023.101370,How does the local area deprivation influence life chances for children in poverty in Wales: A record linkage cohort study.,"Bandyopadhyay A, Whiffen T, Fry R, Brophy S.",,SSM - population health,2023,2023-02-23,Y,Resilience; Cohort study; Education; Deprivation; Child Poverty; Record Linkage; Local Area,,,"

Objectives

Children growing up in poverty are less likely to achieve in school and more likely to experience mental health problems. This study examined factors in the local area that can help a child overcome the negative impact of poverty.

Design

A longitudinal record linkage retrospective cohort study.

Participants

This study included 159,131 children who lived in Wales and completed their age 16 exams (Key Stage 4 (KS4)) between 2009 and 2016. Free School Meal (FSM) provision was used as an indicator of household-level deprivation. Area-level deprivation was measured using the Welsh Index of Multiple Deprivation (WIMD) 2011. An encrypted unique Anonymous Linking Field was used to link the children with their health- and educational records.

Outcome measures

The outcome variable 'Profile to Leave Poverty' (PLP) was constructed based on successful completion of age 16 exams, no mental health condition, no substance and alcohol misuse records in routine data. Logistic regression with stepwise model selection was used to investigate the association between local area deprivation and the outcome variable.

Results

22% of children on FSM achieved PLP compared to 54.9% of non-FSM children. FSM Children from least deprived areas were significantly more likely to achieve PLP (adjusted odds ratio (aOR) - 2.20 (1.93, 2.51)) than FSM children from most deprived areas. FSM children, living in areas with higher community safety, higher relative income, higher access to services, were more likely to achieve PLP than their peers.

Conclusion

The findings indicate that community-level improvements such as increasing safety, connectivity and employment might help in child's education attainment, mental health and reduce risk taking behaviours.",,doi:https://doi.org/10.1016/j.ssmph.2023.101370; html:https://europepmc.org/articles/PMC9986621; pdf:https://europepmc.org/articles/PMC9986621?pdf=render @@ -129,8 +130,8 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 34497074,https://doi.org/10.1136/bmjopen-2020-042483,Modelling the impact of lockdown-easing measures on cumulative COVID-19 cases and deaths in England.,"Ziauddeen H, Subramaniam N, Gurdasani D.",,BMJ open,2021,2021-09-08,Y,Infection control; epidemiology; Public Health; Health Policy,,,"

Objectives

To assess the potential impacts of successive lockdown-easing measures in England, at a point in the COVID-19 pandemic when community transmission levels were relatively high.

Design

We developed a Bayesian model to infer incident cases and reproduction number (R) in England, from incident death data. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points.

Setting

England.

Participants

Publicly available national incident death data for COVID-19 were examined.

Primary outcome

Excess cumulative cases and deaths forecast at 90 days, in simulated scenarios of plausible increases in R after successive easing of lockdown in England, compared with a baseline scenario where R remained constant.

Results

Our model inferred an R of 0.75 on 13 May when England first started easing lockdown. In the most conservative scenario modelled where R increased to 0.80 as lockdown was eased further on 1 June and then remained constant, the model predicted an excess 257 (95% CI 108 to 492) deaths and 26 447 (95% CI 11 105 to 50 549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1), the model predicts 3174 (95% CI 1334 to 6060) excess cumulative deaths and 421 310 (95% CI 177 012 to 804 811) cases. Observed data from the forecasting period aligned most closely to the scenario in which R increased to 0.85 on 1 June, and 0.9 on 4 July.

Conclusions

When levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and healthcare services in England. Following an elimination strategy rather than one of maintenance of R ≤1 would substantially mitigate the impact of the COVID-19 epidemic within England.",,doi:https://doi.org/10.1136/bmjopen-2020-042483; html:https://europepmc.org/articles/PMC8438582; pdf:https://europepmc.org/articles/PMC8438582?pdf=render 36802769,https://doi.org/10.1259/bjr.20201465,Applying machine learning classifiers to automate quality assessment of paediatric dynamic susceptibility contrast (DSC-) MRI data.,"Powell SJ, Withey SB, Sun Y, Grist JT, Novak J, MacPherson L, Abernethy L, Pizer B, Grundy R, Morgan PS, Jaspan T, Bailey S, Mitra D, Auer DP, Avula S, Arvanitis TN, Peet A.",,The British journal of radiology,2023,2023-02-20,Y,,,,"

Objective

Investigate the performance of qualitative review (QR) for assessing dynamic susceptibility contrast (DSC-) MRI data quality in paediatric normal brain and develop an automated alternative to QR.

Methods

1027 signal-time courses were assessed by Reviewer 1 using QR. 243 were additionally assessed by Reviewer 2 and % disagreements and Cohen's κ (κ) were calculated. The signal drop-to-noise ratio (SDNR), root mean square error (RMSE), full width half maximum (FWHM) and percentage signal recovery (PSR) were calculated for the 1027 signal-time courses. Data quality thresholds for each measure were determined using QR results. The measures and QR results trained machine learning classifiers. Sensitivity, specificity, precision, classification error and area under the curve from a receiver operating characteristic curve were calculated for each threshold and classifier.

Results

Comparing reviewers gave 7% disagreements and κ = 0.83. Data quality thresholds of: 7.6 for SDNR; 0.019 for RMSE; 3 s and 19 s for FWHM; and 42.9 and 130.4% for PSR were produced. SDNR gave the best sensitivity, specificity, precision, classification error and area under the curve values of 0.86, 0.86, 0.93, 14.2% and 0.83. Random forest was the best machine learning classifier, giving sensitivity, specificity, precision, classification error and area under the curve of 0.94, 0.83, 0.93, 9.3% and 0.89.

Conclusion

The reviewers showed good agreement. Machine learning classifiers trained on signal-time course measures and QR can assess quality. Combining multiple measures reduces misclassification.

Advances in knowledge

A new automated quality control method was developed, which trained machine learning classifiers using QR results.",,doi:https://doi.org/10.1259/bjr.20201465; html:https://europepmc.org/articles/PMC10161906; pdf:https://europepmc.org/articles/PMC10161906?pdf=render 36497616,https://doi.org/10.3390/ijerph192315544,Association between Internet Usage and Quality of Life of Elderly People in England: Evidence from the English Longitudinal Study of Ageing (ELSA).,"Vidiasratri AR, Bath PA, Bath PA.",,International journal of environmental research and public health,2022,2022-11-23,Y,Internet; Quality of life; Older People,,,"The WHO has stated that the number of senior citizens above age 65 across the world will double by the year 2050: in the UK, the whole population is projected to grow by about 2.5% over a decade, from mid-2018. Although people are living longer, they are not healthier in old age, and there is an increasing number of illnesses and disabilities in the ageing population, which have an impact on their overall well-being and quality of life (QoL). Alongside these trends, Internet technologies have improved and provide a wide range of information, including on medical and health issues. This study aimed to examine the association between the utilisation of the internet among older people in England and their QoL. This study utilised the English Longitudinal Study of Aging (ELSA), a longitudinal study of a representative sample of people aged 50 and over in England. The data from Wave 9 were analysed using bivariate analysis and logistic regression. The results show a strong association between QoL and utilisation of the Internet in older people, even when adjusting for demographic variables and health. Higher use of the internet was associated with older people being less likely to have higher QoL. The excessive use of the internet for communication and gathering information also contributed to lower QoL. From the findings, poorer QoL was also found in people in older age groups, in those who are married, and those who never suffer from chronic diseases. Our findings suggest that the quality of life in older people might not only be associated with the frequency of usage but also the purpose for which the internet is used; however, this relationship is complex and further research should explore this in greater depth. Further research should also investigate how older people's use of the Internet changed during the COVID-19 pandemic and the effects of this on the QoL in older age.",,doi:https://doi.org/10.3390/ijerph192315544; html:https://europepmc.org/articles/PMC9738189; pdf:https://europepmc.org/articles/PMC9738189?pdf=render -36000189,https://doi.org/10.1515/dx-2022-0052,The diagnostic potential and barriers of microbiome based therapeutics.,"Acharjee A, Singh U, Choudhury SP, Gkoutos GV.",,"Diagnosis (Berlin, Germany)",2022,2022-08-25,N,Microbiota; Biomarker; Diagnostics; Machine Learning,,,"High throughput technological innovations in the past decade have accelerated research into the trillions of commensal microbes in the gut. The 'omics' technologies used for microbiome analysis are constantly evolving, and large-scale datasets are being produced. Despite of the fact that much of the research is still in its early stages, specific microbial signatures have been associated with the promotion of cancer, as well as other diseases such as inflammatory bowel disease, neurogenerative diareses etc. It has been also reported that the diversity of the gut microbiome influences the safety and efficacy of medicines. The availability and declining sequencing costs has rendered the employment of RNA-based diagnostics more common in the microbiome field necessitating improved data-analytical techniques so as to fully exploit all the resulting rich biological datasets, while accounting for their unique characteristics, such as their compositional nature as well their heterogeneity and sparsity. As a result, the gut microbiome is increasingly being demonstrating as an important component of personalised medicine since it not only plays a role in inter-individual variability in health and disease, but it also represents a potentially modifiable entity or feature that may be addressed by treatments in a personalised way. In this context, machine learning and artificial intelligence-based methods may be able to unveil new insights into biomedical analyses through the generation of models that may be used to predict category labels, and continuous values. Furthermore, diagnostic aspects will add value in the identification of the non invasive markers in the critical diseases like cancer.",,doi:https://doi.org/10.1515/dx-2022-0052 35140406,https://doi.org/10.1038/s41591-022-01701-w,Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil.,"Cerqueira-Silva T, Katikireddi SV, de Araujo Oliveira V, Flores-Ortiz R, Júnior JB, Paixão ES, Robertson C, Penna GO, Werneck GL, Barreto ML, Pearce N, Sheikh A, Barral-Netto M, Boaventura VS.",,Nature medicine,2022,2022-02-09,Y,,,,"There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.",,doi:https://doi.org/10.1038/s41591-022-01701-w; html:https://europepmc.org/articles/PMC9018414; pdf:https://europepmc.org/articles/PMC9018414?pdf=render +36000189,https://doi.org/10.1515/dx-2022-0052,The diagnostic potential and barriers of microbiome based therapeutics.,"Acharjee A, Singh U, Choudhury SP, Gkoutos GV.",,"Diagnosis (Berlin, Germany)",2022,2022-08-25,N,Microbiota; Biomarker; Diagnostics; Machine Learning,,,"High throughput technological innovations in the past decade have accelerated research into the trillions of commensal microbes in the gut. The 'omics' technologies used for microbiome analysis are constantly evolving, and large-scale datasets are being produced. Despite of the fact that much of the research is still in its early stages, specific microbial signatures have been associated with the promotion of cancer, as well as other diseases such as inflammatory bowel disease, neurogenerative diareses etc. It has been also reported that the diversity of the gut microbiome influences the safety and efficacy of medicines. The availability and declining sequencing costs has rendered the employment of RNA-based diagnostics more common in the microbiome field necessitating improved data-analytical techniques so as to fully exploit all the resulting rich biological datasets, while accounting for their unique characteristics, such as their compositional nature as well their heterogeneity and sparsity. As a result, the gut microbiome is increasingly being demonstrating as an important component of personalised medicine since it not only plays a role in inter-individual variability in health and disease, but it also represents a potentially modifiable entity or feature that may be addressed by treatments in a personalised way. In this context, machine learning and artificial intelligence-based methods may be able to unveil new insights into biomedical analyses through the generation of models that may be used to predict category labels, and continuous values. Furthermore, diagnostic aspects will add value in the identification of the non invasive markers in the critical diseases like cancer.",,doi:https://doi.org/10.1515/dx-2022-0052 36630477,https://doi.org/10.1371/journal.pmed.1004156,Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study.,"Cerqueira-Silva T, Shah SA, Robertson C, Sanchez M, Katikireddi SV, de Araujo Oliveira V, Paixão ES, Rudan I, Junior JB, Penna GO, Pearce N, Werneck GL, Barreto ML, Boaventura VS, Sheikh A, Barral-Netto M.",,PLoS medicine,2023,2023-01-11,Y,,,,"

Background

Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron's emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear.

Methods and findings

Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, ≥65). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], p < 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p < 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p < 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p < 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p < 0.001) and 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose.

Conclusions

We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months.",,doi:https://doi.org/10.1371/journal.pmed.1004156; html:https://europepmc.org/articles/PMC9879484; pdf:https://europepmc.org/articles/PMC9879484?pdf=render 36849590,https://doi.org/10.1038/s41562-023-01522-y,Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.,"Calvert C, Brockway MM, Zoega H, Miller JE, Been JV, Amegah AK, Racine-Poon A, Oskoui SE, Abok II, Aghaeepour N, Akwaowo CD, Alshaikh BN, Ayede AI, Bacchini F, Barekatain B, Barnes R, Bebak K, Berard A, Bhutta ZA, Brook JR, Bryan LR, Cajachagua-Torres KN, Campbell-Yeo M, Chu DT, Connor KL, Cornette L, Cortés S, Daly M, Debauche C, Dedeke IOF, Einarsdóttir K, Engjom H, Estrada-Gutierrez G, Fantasia I, Fiorentino NM, Franklin M, Fraser A, Gachuno OW, Gallo LA, Gissler M, Håberg SE, Habibelahi A, Häggström J, Hookham L, Hui L, Huicho L, Hunter KJ, Huq S, Kc A, Kadambari S, Kelishadi R, Khalili N, Kippen J, Le Doare K, Llorca J, Magee LA, Magnus MC, Man KKC, Mburugu PM, Mediratta RP, Morris AD, Muhajarine N, Mulholland RH, Bonnard LN, Nakibuuka V, Nassar N, Nyadanu SD, Oakley L, Oladokun A, Olayemi OO, Olutekunbi OA, Oluwafemi RO, Ogunkunle TO, Orton C, Örtqvist AK, Ouma J, Oyapero O, Palmer KR, Pedersen LH, Pereira G, Pereyra I, Philip RK, Pruski D, Przybylski M, Quezada-Pinedo HG, Regan AK, Rhoda NR, Rihs TA, Riley T, Rocha TAH, Rolnik DL, Saner C, Schneuer FJ, Souter VL, Stephansson O, Sun S, Swift EM, Szabó M, Temmerman M, Tooke L, Urquia ML, von Dadelszen P, Wellenius GA, Whitehead C, Wong ICK, Wood R, Wróblewska-Seniuk K, Yeboah-Antwi K, Yilgwan CS, Zawiejska A, Sheikh A, Rodriguez N, Burgner D, Stock SJ, Azad MB.",,Nature human behaviour,2023,2023-02-27,Y,,,,"Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.",,doi:https://doi.org/10.1038/s41562-023-01522-y; html:https://europepmc.org/articles/PMC10129868; pdf:https://europepmc.org/articles/PMC10129868?pdf=render 37124948,https://doi.org/10.1016/j.lanepe.2023.100638,Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland.,"Robertson C, Kerr S, Sheikh A.",,The Lancet regional health. Europe,2023,2023-04-14,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render @@ -149,8 +150,8 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 33827854,https://doi.org/10.1136/bmj.n826,Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource.,"Wood A, Denholm R, Hollings S, Cooper J, Ip S, Walker V, Denaxas S, Akbari A, Banerjee A, Whiteley W, Lai A, Sterne J, Sudlow C, CVD-COVID-UK consortium.",,BMJ (Clinical research ed.),2021,2021-04-07,Y,,,,"

Objective

To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust.

Design

Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital's new trusted research environment.

Setting

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

Participants

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

Main measures of interest

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

Results

The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one.

Conclusions

This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research.",,doi:https://doi.org/10.1136/bmj.n826; html:https://europepmc.org/articles/PMC8413899; pdf:https://europepmc.org/articles/PMC8413899?pdf=render 36580462,https://doi.org/10.1371/journal.pone.0279381,Investigating the potential impact of PCSK9-inhibitors on mood disorders using eQTL-based Mendelian randomization.,"Aman A, Slob EAW, Ward J, Cullen B, Graham N, Lyall DM, Sattar N, Strawbridge RJ.",,PloS one,2022,2022-12-29,Y,,,,"Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2x10-5-0.03), and neuroticism score (p-value range = 2.9x10-5-0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.",,doi:https://doi.org/10.1371/journal.pone.0279381; html:https://europepmc.org/articles/PMC9799310; pdf:https://europepmc.org/articles/PMC9799310?pdf=render 36997856,https://doi.org/10.1186/s12882-023-03126-0,A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,BMC nephrology,2023,2023-03-30,Y,Mortality; Frailty; Haemodialysis; Hospitalisation; Clinical Frailty Scale,,,"

Background

The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality.

Methods

We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists.

Results

453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P < 0.001) on raw frailty scores and minimal agreement (Cohen's κ = 0.274, P < 0.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P = 0.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P = 0.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P = 0.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P = 0.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P < 0.001).

Conclusions

Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis.

Trial registration

Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",,doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render -37586846,https://doi.org/10.1136/openhrt-2023-002378,Cardiovascular imaging research priorities.,"MacArthur JAL, Yong GL, Dweck MR, Fairbairn TA, Weir-McCall J, Puyol-Antón E, Meldrum J, Blakelock P, Khan S, Morrice L, Sudlow CLM, Williams MC.",,Open heart,2023,2023-08-01,Y,Health Services; Research Design; Diagnostic Imaging,,,"

Objectives

Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research.

Methods

First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner.

Results

The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey.

Conclusions

We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.",,doi:https://doi.org/10.1136/openhrt-2023-002378; html:https://europepmc.org/articles/PMC10432634; pdf:https://europepmc.org/articles/PMC10432634?pdf=render 36369151,https://doi.org/10.1038/s41467-022-34244-2,"Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England.","Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott P.",,Nature communications,2022,2022-11-11,Y,,,,"Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study monitored the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.",,doi:https://doi.org/10.1038/s41467-022-34244-2; html:https://europepmc.org/articles/PMC9651890; pdf:https://europepmc.org/articles/PMC9651890?pdf=render +37586846,https://doi.org/10.1136/openhrt-2023-002378,Cardiovascular imaging research priorities.,"MacArthur JAL, Yong GL, Dweck MR, Fairbairn TA, Weir-McCall J, Puyol-Antón E, Meldrum J, Blakelock P, Khan S, Morrice L, Sudlow CLM, Williams MC.",,Open heart,2023,2023-08-01,Y,Health Services; Research Design; Diagnostic Imaging,,,"

Objectives

Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research.

Methods

First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner.

Results

The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey.

Conclusions

We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.",,doi:https://doi.org/10.1136/openhrt-2023-002378; html:https://europepmc.org/articles/PMC10432634; pdf:https://europepmc.org/articles/PMC10432634?pdf=render 34384736,https://doi.org/10.1016/s2589-7500(21)00175-8,"Predicted COVID-19 positive cases, hospitalisations, and deaths associated with the Delta variant of concern, June-July, 2021.","Shah SA, Moore E, Robertson C, McMenamin J, Katikireddi SV, Simpson CR, Shi T, Agrawal U, McCowan C, Stock S, Ritchie LD, Sheikh A, Public Health Scotland and the EAVE II Collaborators.",,The Lancet. Digital health,2021,2021-08-09,Y,,,,,,doi:https://doi.org/10.1016/S2589-7500(21)00175-8; html:https://europepmc.org/articles/PMC8352493; pdf:https://europepmc.org/articles/PMC8352493?pdf=render 35024157,https://doi.org/10.1177/20552076211059350,Digitally enabled flash glucose monitoring for inpatients with COVID-19: Feasibility and pilot implementation in a teaching NHS Hospital in the UK.,"Robbins T, Hopper A, Brophy J, Pearson E, Suthantirakumar R, Vankad M, Igharo N, Baitule S, Clark CC, Arvanitis TN, Sankar S, Kyrou I, Randeva H.",,Digital health,2022,2022-01-07,Y,Diabetes; Inpatient Care; Digital Health; Flash Glucose Monitoring; Covid-19,,,"

Background

COVID-19 placed significant challenges on healthcare systems. People with diabetes are at high risk of severe COVID-19 with poor outcomes. We describe the first reported use of inpatient digital flash glucose monitoring devices in a UK NHS hospital to support management of people with diabetes hospitalized for COVID-19.

Methods

Inpatients at University Hospitals Coventry & Warwickshire (UHCW) NHS Trust with COVID-19 and diabetes were considered for digitally enabled flash glucose monitoring during their hospitalization. Glucose monitoring data were analysed, and potential associations were explored between relevant parameters, including time in hypoglycaemia, hyperglycaemia, and in range, glycated haemoglobin (HbA1c), average glucose, body mass index (BMI), and length of stay.

Results

During this pilot, digital flash glucose monitoring devices were offered to 25 inpatients, of whom 20 (type 2/type 1: 19/1; mean age: 70.6 years; mean HbA1c: 68.2 mmol/mol; mean BMI: 28.2 kg/m2) accepted and used these (80% uptake). In total, over 2788 h of flash glucose monitoring were recorded for these inpatients with COVID-19 and diabetes. Length of stay was not associated with any of the studied variables (all p-values >0.05). Percentage of time in hyperglycaemia exhibited significant associations with both percentage of time in hypoglycaemia and percentage of time in range, as well as with HbA1c (all p-values <0.05). The average glucose was significantly associated with percentage of time in hypoglycaemia, percentage of time in range, and HbA1c (all p-values <0.05).

Discussion

We report the first pilot inpatient use of digital flash glucose monitors in an NHS hospital to support care of inpatients with diabetes and COVID-19. Overall, there are strong arguments for the inpatient use of these devices in the COVID-19 setting, and the findings of this pilot demonstrate feasibility of this digitally enabled approach and support wider use for inpatients with diabetes and COVID-19.",,doi:https://doi.org/10.1177/20552076211059350; html:https://europepmc.org/articles/PMC8744149; pdf:https://europepmc.org/articles/PMC8744149?pdf=render 36426419,https://doi.org/10.1111/hsc.14109,"""I don't mean to be rude, but could you put a mask on while I'm here?"" A qualitative study of risks experienced by domiciliary care workers in Wales during the COVID-19 pandemic. ","Prout H, Lugg-Widger FV, Brookes-Howell L, Cannings-John R, Akbari A, John A, Thomas DR, Robling M.",,Health & social care in the community,2022,2022-11-24,Y,,,,"Domiciliary care workers (DCWs) continued to provide care to adults in their own homes throughout the COVID-19 pandemic. The evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed. The OSCAR study will quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, explore causes of variation and extrapolate to the rest of the UK DCW population. An embedded qualitative study aimed to explore DCW experiences during the pandemic, including factors that may have varied risk of exposure to COVID-19 and adverse health and wellbeing outcomes. Registered DCWs working throughout Wales were invited to participate in a semi-structured telephone interview. 24 DCWs were interviewed between February and July 2021. Themes were identified through inductive analysis using thematic coding. Several themes emerged relating to risk of exposure to COVID-19. First, general changes to the role of the DCW during the pandemic were identified. Second, practical challenges for DCWs in the workplace were reported, including staff shortages, clients and families not following safety procedures, initial shortages of personal protective equipment (PPE), DCW criticism of standard use PPE, client difficulty with PPE and management of rapid antigen testing. Third, lack of government/employer preparation for a pandemic was described, including the reorganisation of staff clients and services, inadequate or confusing information for many DCWs, COVID-19 training and the need for improved practical instruction and limited official standard risk assessments for DCWs. Pressure to attend work and perceptions of COVID-19 risk and vaccination was also reported. In summary, this paper describes the risk factors associated with working during the pandemic. We have mapped recommendations for each problem using these qualitative findings including tailored training and better support for isolated team members and identified the required changes at several socio-ecological levels.",,doi:https://doi.org/10.1111/hsc.14109; html:https://europepmc.org/articles/PMC10100139; pdf:https://europepmc.org/articles/PMC10100139?pdf=render; doi:https://doi.org/10.1111/hsc.14109 @@ -180,8 +181,8 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 35027756,https://doi.org/10.1038/s41591-021-01666-2,SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland.,"Stock SJ, Carruthers J, Calvert C, Denny C, Donaghy J, Goulding A, Hopcroft LEM, Hopkins L, McLaughlin T, Pan J, Shi T, Taylor B, Agrawal U, Auyeung B, Katikireddi SV, McCowan C, Murray J, Simpson CR, Robertson C, Vasileiou E, Sheikh A, Wood R.",,Nature medicine,2022,2022-01-13,Y,,,,"Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18-44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1-6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5-99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.",,doi:https://doi.org/10.1038/s41591-021-01666-2; html:https://europepmc.org/articles/PMC8938271; pdf:https://europepmc.org/articles/PMC8938271?pdf=render 34217220,https://doi.org/10.1186/s12872-021-02137-9,Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19.,"O'Gallagher K, Shek A, Bean DM, Bendayan R, Papachristidis A, Teo JTH, Dobson RJB, Shah AM, Zakeri R.",,BMC cardiovascular disorders,2021,2021-07-03,Y,Hypertension; Diabetes; Cardiovascular disease; Cardiovascular risk factors; Covid-19,,,"

Background

The relative association between cardiovascular (CV) risk factors, such as diabetes and hypertension, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear.

Methods

We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1st March and 30th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained.

Results

Among 1721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients < 70 years of age (adjusted HR 2.43 [95% CI 1.16-5.07]), but not in those ≥ 70 years (aHR 1.14 [95% CI 0.77-1.69]). RF-CVD were not independently associated with mortality in either age group (< 70 y aHR 1.21 [95% CI 0.72-2.01], ≥ 70 y aHR 1.07 [95% CI 0.76-1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p < 0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE.

Conclusions

In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group. Trial registration n/a.",,doi:https://doi.org/10.1186/s12872-021-02137-9; html:https://europepmc.org/articles/PMC8254437; pdf:https://europepmc.org/articles/PMC8254437?pdf=render 35715350,https://doi.org/10.1016/j.vaccine.2022.06.010,Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform.,"Walker JL, Schultze A, Tazare J, Tamborska A, Singh B, Donegan K, Stowe J, Morton CE, Hulme WJ, Curtis HJ, Williamson EJ, Mehrkar A, Eggo RM, Rentsch CT, Mathur R, Bacon S, Walker AJ, Davy S, Evans D, Inglesby P, Hickman G, MacKenna B, Tomlinson L, Ca Green A, Fisher L, Cockburn J, Parry J, Hester F, Harper S, Bates C, Evans SJ, Solomon T, Andrews NJ, Douglas IJ, Goldacre B, Smeeth L, McDonald HI.",,Vaccine,2022,2022-06-07,Y,Transverse Myelitis; Guillain-barré Syndrome; Vaccine Safety; Self-controlled Case Series; Bell’s Palsy; Covid-19 Vaccines,,,"

Introduction

We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy.

Methods

With the approval of NHS England we analysed primary care data from >17 million patients in England linked to emergency care, hospital admission and mortality records in the OpenSAFELY platform. Separately for each vaccine brand, we used a self-controlled case series design to estimate the incidence rate ratio for each outcome in the period following vaccination (4-42 days for GBS, 4-28 days for transverse myelitis and Bell's palsy) compared to a within-person baseline, using conditional Poisson regression.

Results

Among 7,783,441 ChAdOx1 vaccinees, there was an increased rate of GBS (N = 517; incidence rate ratio 2·85; 95% CI2·33-3·47) and Bell's palsy (N = 5,350; 1·39; 1·27-1·53) following a first dose of ChAdOx1 vaccine, corresponding to 11.0 additional cases of GBS and 17.9 cases of Bell's palsy per 1 million vaccinees if causal. For GBS this applied to the first, but not the second, dose. There was no clear evidence of an association of ChAdOx1 vaccination with transverse myelitis (N = 199; 1·51; 0·96-2·37). Among 5,729,152 BNT162b2 vaccinees, there was no evidence of any association with GBS (N = 283; 1·09; 0·75-1·57), transverse myelitis (N = 109; 1·62; 0·86-3·03) or Bell's palsy (N = 3,609; 0·89; 0·76-1·03). Among 255,446 mRNA-1273 vaccine recipients there was no evidence of an association with Bell's palsy (N = 78; 0·88, 0·32-2·42).

Conclusions

COVID-19 vaccines save lives, but it is important to understand rare adverse events. We observed a short-term increased rate of Guillain-Barré syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.",,doi:https://doi.org/10.1016/j.vaccine.2022.06.010; html:https://europepmc.org/articles/PMC9170533; pdf:https://europepmc.org/articles/PMC9170533?pdf=render -37463814,https://doi.org/10.1136/bmjopen-2022-069635,HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.,"Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.",,BMJ open,2023,2023-07-18,Y,Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care,,,"

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.",,doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render 34670038,https://doi.org/10.1056/nejmc2113864,BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant.,"Sheikh A, Robertson C, Taylor B.",,The New England journal of medicine,2021,2021-10-20,Y,,,,,,doi:https://doi.org/10.1056/NEJMc2113864; html:https://europepmc.org/articles/PMC8552534; pdf:https://europepmc.org/articles/PMC8552534?pdf=render +37463814,https://doi.org/10.1136/bmjopen-2022-069635,HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.,"Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.",,BMJ open,2023,2023-07-18,Y,Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care,,,"

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.",,doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render 37147628,https://doi.org/10.1186/s12911-023-02181-9,Ontology-driven and weakly supervised rare disease identification from clinical notes.,"Dong H, Suárez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",,BMC medical informatics and decision making,2023,2023-05-05,Y,Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision,,,"

Background

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods

We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results

The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion

The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",,doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render 36653750,https://doi.org/10.1186/s12882-022-03043-8,Ultrasound quadriceps muscle thickness is variably associated with frailty in haemodialysis recipients.,"Anderson BM, Wilson DV, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,BMC nephrology,2023,2023-01-18,Y,Frailty; ultrasound; epidemiology; Sarcopenia,,,"

Background

Ultrasonographic quantitation of quadriceps muscle mass is increasingly used for assessment of sarcopenia, but its relationship with frailty in haemodialysis recipients is not known. This study explores the relationship between ultrasound-derived bilateral anterior thigh thickness (BATT), sarcopenia, and frailty by common frailty tools (Frailty Phenotype [FP], Frailty Index [FI], Edmonton Frailty [EFS], and Clinical Frailty Scale [CFS]).

Methods

This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis recipients deeply phenotyped for frailty. Ultrasound assessment of BATT was obtained with participants at an angle of ≤45°, with legs outstretched and knees resting at 10°-20°, according to an established protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, Low Muscle Mass (LMM), and sarcopenia with stepwise adjustment for a priori covariables.

Results

In total 223 study participants had ultrasound measurements. Frailty ranged from 34% for FP to 58% for FI. BATT was associated with increasing frailty on simple linear regression by all frailty tools, but lost significance on addition of covariables. Upon dichotomising frailty tools into Frail/Not Frail, BATT was associated with frailty by all tools on univariable analyses, but only retained association for EFS on the fully adjusted model (OR 0.97, 95% C.I. 0.94-1.00, P = 0.05).

Conclusions

Ultrasound measures of quadriceps thickness is variably associated with frailty in prevalent haemodialysis recipients, dependent upon the frailty tool used, but not independent of other variables. Further work is required to establish the added value of sarcopenia measurement in frail haemodialysis patients.

Trial registration

Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",,doi:https://doi.org/10.1186/s12882-022-03043-8; html:https://europepmc.org/articles/PMC9847024; pdf:https://europepmc.org/articles/PMC9847024?pdf=render 34861180,https://doi.org/10.1016/s2213-2600(21)00491-4,Risk of COVID-19 hospital admission among children aged 5-17 years with asthma in Scotland: a national incident cohort study.,"Shi T, Pan J, Katikireddi SV, McCowan C, Kerr S, Agrawal U, Shah SA, Simpson CR, Ritchie LD, Robertson C, Sheikh A, Public Health Scotland and the EAVE II Collaborators.",,The Lancet. Respiratory medicine,2022,2021-11-30,Y,,,,"

Background

There is an urgent need to inform policy deliberations about whether children with asthma should be vaccinated against SARS-CoV-2 and, if so, which subset of children with asthma should be prioritised. We were asked by the UK's Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which children with asthma were at increased risk of serious COVID-19 outcomes.

Methods

This national incident cohort study was done in all children in Scotland aged 5-17 years who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). We used data from EAVE II to investigate the risk of COVID-19 hospitalisation among children with markers of uncontrolled asthma defined by either previous asthma hospital admission or oral corticosteroid prescription in the previous 2 years. A Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% CIs for the association between asthma and COVID-19 hospital admission, stratified by markers of asthma control (previous asthma hospital admission and number of previous prescriptions for oral corticosteroids within 2 years of the study start date). Analyses were adjusted for age, sex, socioeconomic status, comorbidity, and previous hospital admission.

Findings

Between March 1, 2020, and July 27, 2021, 752 867 children were included in the EAVE II dataset, 63 463 (8·4%) of whom had clinician-diagnosed-and-recorded asthma. Of these, 4339 (6·8%) had RT-PCR confirmed SARS-CoV-2 infection. In those with confirmed infection, 67 (1·5%) were admitted to hospital with COVID-19. Among the 689 404 children without asthma, 40 231 (5·8%) had confirmed SARS-CoV-2 infections, of whom 382 (0·9%) were admitted to hospital with COVID-19. The rate of COVID-19 hospital admission was higher in children with poorly controlled asthma than in those with well controlled asthma or without asthma. When using previous hospital admission for asthma as the marker of uncontrolled asthma, the adjusted HR was 6·40 (95% CI 3·27-12·53) for those with poorly controlled asthma and 1·36 (1·02-1·80) for those with well controlled asthma, compared with those with no asthma. When using oral corticosteroid prescriptions as the marker of uncontrolled asthma, the adjusted HR was 3·38 (1·84-6·21) for those with three or more prescribed courses of corticosteroids, 3·53 (1·87-6·67) for those with two prescribed courses of corticosteroids, 1·52 (0·90-2·57) for those with one prescribed course of corticosteroids, and 1·34 (0·98-1·82) for those with no prescribed course, compared with those with no asthma.

Interpretation

School-aged children with asthma with previous recent hospital admission or two or more courses of oral corticosteroids are at markedly increased risk of COVID-19 hospital admission and should be considered a priority for vaccinations. This would translate into 9124 children across Scotland and an estimated 109 448 children across the UK.

Funding

UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and Scottish Government.",,doi:https://doi.org/10.1016/S2213-2600(21)00491-4; html:https://europepmc.org/articles/PMC8631918 @@ -192,14 +193,14 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 35913410,https://doi.org/10.1093/cid/ciac629,Validity of Self-testing at Home With Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Detection by Lateral Flow Immunoassay.,"Atchison CJ, Moshe M, Brown JC, Whitaker M, Wong NCK, Bharath AA, McKendry RA, Darzi A, Ashby D, Donnelly CA, Riley S, Elliott P, Barclay WS, Cooke GS, Ward H.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2023,2023-02-01,Y,Antibodies; Lateral Flow Immunoassay; Home-testing; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ECLIA with virus neutralization.",,doi:https://doi.org/10.1093/cid/ciac629; html:https://europepmc.org/articles/PMC9384551; pdf:https://europepmc.org/articles/PMC9384551?pdf=render 35973468,https://doi.org/10.1016/j.jviromet.2022.114607,Evaluation of the impact of pre-analytical conditions on sample stability for the detection of SARS-CoV-2 RNA.,"Mosscrop L, Watber P, Elliot P, Cooke G, Barclay W, Freemont PS, Rosadas C, Taylor GP.",,Journal of virological methods,2022,2022-08-13,Y,RNA; Diagnosis; Rt-qpcr; Sample Stability; Sars-cov-2,,,"Demand for accurate SARS-CoV-2 diagnostics is high. Most samples in the UK are collected in the community and rely on the postal service for delivery to the laboratories. The current recommendation remains that swabs should be collected in Viral Transport Media (VTM) and transported with a cold chain to the laboratory for RNA extraction and RT-qPCR. This is not always possible. We aimed to test the stability of SARS-CoV-2 RNA subjected to different pre-analytical conditions. Swabs were dipped into PBS containing cultured SARS-CoV-2 and placed in either a dry tube or a tube containing either normal saline or VTM. The tubes were then stored at different temperatures (20-50 °C) for variable periods (8 h to 5 days). Samples were tested by RT-qPCR targeting SARS-CoV-2 E gene. VTM outperformed swabs in saline and dry swabs in all conditions. Samples in VTM were stable, independent of a cold chain, for 5 days, with a maximum increase in cycle threshold (Ct) of 1.34 when held at 40 °C. Using normal saline as the transport media resulted in a loss of sensitivity (increased Ct) over time and with increasing temperature (up to 7.8 cycles compared to VTM). SARS-CoV-2 was not detected in 3/9 samples in normal saline when tested after 120 h incubation. Transportation of samples in VTM provides a high level of confidence in the results despite the potential for considerable, uncontrolled variation in temperature and longer transportation periods. False negative results may be seen after 96 h in saline and viral loads will appear lower.",,doi:https://doi.org/10.1016/j.jviromet.2022.114607; html:https://europepmc.org/articles/PMC9374597; pdf:https://europepmc.org/articles/PMC9374597?pdf=render 34942103,https://doi.org/10.1016/s0140-6736(21)02754-9,"Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.","Katikireddi SV, Cerqueira-Silva T, Vasileiou E, Robertson C, Amele S, Pan J, Taylor B, Boaventura V, Werneck GL, Flores-Ortiz R, Agrawal U, Docherty AB, McCowan C, McMenamin J, Moore E, Ritchie LD, Rudan I, Shah SA, Shi T, Simpson CR, Barreto ML, Oliveira VA, Barral-Netto M, Sheikh A.",,"Lancet (London, England)",2022,2021-12-20,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670 -37358897,https://doi.org/10.2196/45849,Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.,"Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.",,JMIR formative research,2023,2023-06-26,Y,Pain; Mental health; Annotation; Information Extraction; Natural Language Processing,,,"

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.",,doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render; doi:https://doi.org/10.2196/45849 36629015,https://doi.org/10.1177/17407745221143449,Lack of transparent reporting of trial monitoring approaches in randomised controlled trials: A systematic review of contemporary protocol papers.,"Hsieh SF, Yorke-Edwards V, Murray ML, Diaz-Montana C, Love SB, Sydes MR.",,"Clinical trials (London, England)",2023,2023-01-11,Y,Systematic review; Randomised Controlled Trial; On-site Monitoring; Risk-based Monitoring; Protocol Paper; Central Monitoring; Trial Monitoring; Reporting Monitoring,,,"

Background

Monitoring is essential to ensure patient safety and data integrity in clinical trials as per Good Clinical Practice. The Standard Protocol Items: Recommendations for Interventional Trials Statement and its checklist guides authors to include monitoring in their protocols. We investigated how well monitoring was reported in published 'protocol papers' for contemporary randomised controlled trials.

Methods

A systematic search was conducted in PubMed to identify eligible protocol papers published in selected journals between 1 January 2020 and 31 May 2020. Protocol papers were classified by whether they reported monitoring and, if so, by the details of monitoring. Data were summarised descriptively.

Results

Of 811 protocol papers for randomised controlled trials, 386 (48%; 95% CI: 44%-51%) explicitly reported some monitoring information. Of these, 20% (77/386) reported monitoring information consistent with an on-site monitoring approach, and 39% (152/386) with central monitoring, 26% (101/386) with a mixed approach, while 14% (54/386) did not provide sufficient information to specify an approach. Only 8% (30/386) of randomised controlled trials reported complete details about all of scope, frequency and organisation of monitoring; frequency of monitoring was the least reported. However, 6% (25/386) of papers used the term 'audit' to describe 'monitoring'.

Discussion

Monitoring information was reported in only approximately half of the protocol papers. Suboptimal reporting of monitoring hinders the clinical community from having the full information on which to judge the validity of a trial and jeopardises the value of protocol papers and the credibility of the trial itself. Greater efforts are needed to promote the transparent reporting of monitoring to journal editors and authors.",,doi:https://doi.org/10.1177/17407745221143449; html:https://europepmc.org/articles/PMC10021127; pdf:https://europepmc.org/articles/PMC10021127?pdf=render +37358897,https://doi.org/10.2196/45849,Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.,"Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.",,JMIR formative research,2023,2023-06-26,Y,Pain; Mental health; Annotation; Information Extraction; Natural Language Processing,,,"

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.",,doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render; doi:https://doi.org/10.2196/45849 35511729,https://doi.org/10.1093/ageing/afac084,"COVID-19 risk factors amongst 14,786 care home residents: an observational longitudinal analysis including daily community positive test rates of COVID-19, hospital stays and vaccination status in Wales (UK) between 1 September 2020 and 1 May 2021. ","Hollinghurst J, Hollinghurst R, North L, Mizen A, Akbari A, Long S, Lyons RA, Fry R.",,Age and ageing,2022,2022-05-01,Y,,,,"COVID-19 vaccinations have been prioritised for high risk individuals. Determine individual-level risk factors for care home residents testing positive for SARS-CoV-2. Longitudinal observational cohort study using individual-level linked data from the Secure Anonymised Information Linkage (SAIL) databank. Fourteen thousand seven hundred and eighty-six older care home residents (aged 65+) living in Wales between 1 September 2020 and 1 May 2021. Our dataset consisted of 2,613,341 individual-level daily observations within 697 care homes. We estimated odds ratios (ORs [95% confidence interval]) using multilevel logistic regression models. Our outcome of interest was a positive SARS-CoV-2 PCR test. We included time-dependent covariates for the estimated community positive test rate of COVID-19, hospital inpatient status, vaccination status and frailty. Additional covariates were included for age, sex and specialist care home services. The multivariable regression model indicated an increase in age (OR 1.01 [1.00,1.01] per year), community positive test rate (OR 1.13 [1.12,1.13] per percent increase), hospital inpatients (OR 7.40 [6.54,8.36]), and residents in care homes with non-specialist dementia care (OR 1.42 [1.01,1.99]) had an increased odds of a positive test. Having a positive test prior to the observation period (OR 0.58 [0.49,0.68]) and either one or two doses of a vaccine (0.21 [0.17,0.25] and 0.05 [0.02,0.09], respectively) were associated with a decreased odds. Care providers need to remain vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable. Minimising potential COVID-19 infection for care home residents when admitted to hospital should be prioritised.",,doi:https://doi.org/10.1093/ageing/afac084; html:https://europepmc.org/articles/PMC9070807; pdf:https://europepmc.org/articles/PMC9070807?pdf=render 35502909,https://doi.org/10.1177/01410768221095239,Impact on emergency and elective hospital-based care in Scotland over the first 12 months of the pandemic: interrupted time-series analysis of national lockdowns.,"Shah SA, Mulholland RH, Wilkinson S, Katikireddi SV, Pan J, Shi T, Kerr S, Agrawal U, Rudan I, Simpson CR, Stock SJ, Macleod J, Murray JL, McCowan C, Ritchie L, Woolhouse M, Sheikh A.",,Journal of the Royal Society of Medicine,2022,2022-05-03,Y,Public Health; Statistics And Research Methods; Population Trends,,,"

Objectives

COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic.

Design

We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020-28 March 2021.

Setting

Scotland, UK.

Participants

Patients receiving hospital care from NHS Scotland.

Main outcome measures

We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019.

Results

As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: -1.98% (-2.38, -1.58) in accident and emergency attendance, -1.36% (-1.68, -1.04) in emergency admissions and -2.31% (-2.95, -1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0-14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period.

Conclusions

We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.",,doi:https://doi.org/10.1177/01410768221095239; html:https://europepmc.org/articles/PMC9723811; pdf:https://europepmc.org/articles/PMC9723811?pdf=render 37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render -36219788,https://doi.org/10.1093/ije/dyac185,Borrowing strength from clinical trials in analysing longitudinal data from a treated cohort: investigating the effectiveness of acetylcholinesterase inhibitors in the management of dementia.,"Knight R, Stewart R, Khondoker M, Landau S.",,International journal of epidemiology,2023,2023-06-01,Y,Cognition; Dementia; Randomized controlled trial; acetylcholinesterase inhibitors; Electronic Medical Record; Bayesian Modelling,,,"

Background

Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation.

Methods

A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources.

Results

The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12 months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE = 0.316) or cohort data only (1.56, SE = 0.240) overestimated this compared with the estimate using data from both sources (0.86, SE = 0.327).

Conclusions

It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.",,doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render 34104901,https://doi.org/10.1016/s2666-7568(21)00093-3,Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long-term care facilities (VIVALDI): a prospective cohort study.,"Krutikov M, Palmer T, Tut G, Fuller C, Shrotri M, Williams H, Davies D, Irwin-Singer A, Robson J, Hayward A, Moss P, Copas A, Shallcross L.",,The lancet. Healthy longevity,2021,2021-06-03,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(21)00093-3; html:https://europepmc.org/articles/PMC8175048; pdf:https://europepmc.org/articles/PMC8175048?pdf=render; doi:https://doi.org/10.1016/s2666-7568(21)00093-3 34174193,https://doi.org/10.1016/s1473-3099(21)00289-9,Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.,"Shrotri M, Krutikov M, Palmer T, Giddings R, Azmi B, Subbarao S, Fuller C, Irwin-Singer A, Davies D, Tut G, Lopez Bernal J, Moss P, Hayward A, Copas A, Shallcross L.",,The Lancet. Infectious diseases,2021,2021-06-23,Y,,,,"

Background

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination.

Methods

The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421.

Findings

10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001).

Interpretation

Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities.

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738; doi:https://doi.org/10.1016/s1473-3099(21)00289-9 +36219788,https://doi.org/10.1093/ije/dyac185,Borrowing strength from clinical trials in analysing longitudinal data from a treated cohort: investigating the effectiveness of acetylcholinesterase inhibitors in the management of dementia.,"Knight R, Stewart R, Khondoker M, Landau S.",,International journal of epidemiology,2023,2023-06-01,Y,Cognition; Dementia; Randomized controlled trial; acetylcholinesterase inhibitors; Electronic Medical Record; Bayesian Modelling,,,"

Background

Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation.

Methods

A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources.

Results

The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12 months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE = 0.316) or cohort data only (1.56, SE = 0.240) overestimated this compared with the estimate using data from both sources (0.86, SE = 0.327).

Conclusions

It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.",,doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render 35185750,https://doi.org/10.3389/fneur.2021.787107,Physician-Confirmed and Administrative Definitions of Stroke in UK Biobank Reflect the Same Underlying Genetic Trait.,"Rannikmäe K, Rawlik K, Ferguson AC, Avramidis N, Jiang M, Pirastu N, Shen X, Davidson E, Woodfield R, Malik R, Dichgans M, Tenesa A, Sudlow C.",,Frontiers in neurology,2021,2022-02-02,Y,Validation; Genetic correlation; Stroke; Accuracy; Routinely Collected Health Data,,,"

Background

Stroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation.

Methods

We compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants, we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci.

Results

The stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg.81-1) and each other (rg.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definition.

Conclusions

Stroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.",,doi:https://doi.org/10.3389/fneur.2021.787107; html:https://europepmc.org/articles/PMC8847736; pdf:https://europepmc.org/articles/PMC8847736?pdf=render 31783849,https://doi.org/10.1186/s12911-019-0953-2,Developing a standardised approach to the aggregation of inpatient episodes into person-based spells in all specialties and psychiatric specialties.,"Rees S, Akbari A, Collins H, Lee SC, Marchant A, Rees A, Thayer D, Wang T, Wood S, John A.",,BMC medical informatics and decision making,2019,2019-11-29,Y,Data Quality; Data Linkage; Electronic Healthcare Record; Spells; Hospital Inpatient Episodes; Routine Health Data,Improving Public Health,,"

Background

Electronic health record (EHR) data are available for research in all UK nations and cross-nation comparative studies are becoming more common. All UK inpatient EHRs are based around episodes, but episode-based analysis may not sufficiently capture the patient journey. There is no UK-wide method for aggregating episodes into standardised person-based spells. This study identifies two data quality issues affecting the creation of person-based spells, and tests four methods to create these spells, for implementation across all UK nations.

Methods

Welsh inpatient EHRs from 2013 to 2017 were analysed. Phase one described two data quality issues; transfers of care and episode sequencing. Phase two compared four methods for creating person spells. Measures were mean length of stay (LOS, expressed in days) and number of episodes per person spell for each method.

Results

3.5% of total admissions were transfers-in and 3.1% of total discharges were transfers-out. 68.7% of total transfers-in and 48.7% of psychiatric transfers-in had an identifiable preceding transfer-out, and 78.2% of total transfers-out and 59.0% of psychiatric transfers-out had an identifiable subsequent transfer-in. 0.2% of total episodes and 4.0% of psychiatric episodes overlapped with at least one other episode of any specialty. Method one (no evidence of transfer required; overlapping episodes grouped together) resulted in the longest mean LOS (4.0 days for all specialties; 48.5 days for psychiatric specialties) and the fewest single episode person spells (82.4% of all specialties; 69.7% for psychiatric specialties). Method three (evidence of transfer required; overlapping episodes separated) resulted in the shortest mean LOS (3.7 days for all specialties; 45.8 days for psychiatric specialties) and the most single episode person spells; (86.9% for all specialties; 86.3% for psychiatric specialties).

Conclusions

Transfers-in appear better recorded than transfers-out. Transfer coding is incomplete, particularly for psychiatric specialties. The proportion of episodes that overlap is small but psychiatric episodes are disproportionately affected. The most successful method for grouping episodes into person spells aggregated overlapping episodes and required no evidence of transfer from admission source/method or discharge destination codes. The least successful method treated overlapping episodes as distinct and required transfer coding. The impact of all four methods was greater for psychiatric specialties.","Rees et al used a Welsh database to examine inpatient episode/transfer coding coding for psychiatric patients. They identified deficiencies in the existing coding system for psychitatrics transfers and unexplained coding mistakes/problems, then they presesnt several different methods for constructing the inpatient spell to improve coding and avoid misclassification.",doi:https://doi.org/10.1186/s12911-019-0953-2; html:https://europepmc.org/articles/PMC6884917; pdf:https://europepmc.org/articles/PMC6884917?pdf=render 37607793,https://doi.org/10.1136/bmjopen-2023-076296,"Knowledge support for optimising antibiotic prescribing for common infections in general practices: evaluation of the effectiveness of periodic feedback, decision support during consultations and peer comparisons in a cluster randomised trial (BRIT2) - study protocol.","van Staa T, Sharma A, Palin V, Fahmi A, Cant H, Zhong X, Jury F, Gold N, Welfare W, Ashcroft D, Tsang JY, Elliott RA, Sutton C, Armitage C, Couch P, Moulton G, Tempest E, Buchan IE.",,BMJ open,2023,2023-08-22,Y,Infectious diseases; Randomized controlled trial; Primary Care; Electronic Health Records,,,"

Introduction

This project applies a Learning Healthcare System (LHS) approach to antibiotic prescribing for common infections in primary care. The approach involves iterations of data analysis, feedback to clinicians and implementation of quality improvement activities by the clinicians. The main research question is, can a knowledge support system (KSS) intervention within an LHS implementation improve antibiotic prescribing without increasing the risk of complications?

Methods and analysis

A pragmatic cluster randomised controlled trial will be conducted, with randomisation of at least 112 general practices in North-West England. General practices participating in the trial will be randomised to the following interventions: periodic practice-level and individual prescriber feedback using dashboards; or the same dashboards plus a KSS. Data from large databases of healthcare records are used to characterise heterogeneity in antibiotic uses, and to calculate risk scores for clinical outcomes and for the effectiveness of different treatment strategies. The results provide the baseline content for the dashboards and KSS. The KSS comprises a display within the electronic health record used during the consultation; the prescriber (general practitioner or allied health professional) will answer standard questions about the patient's presentation and will then be presented with information (eg, patient's risk of complications from the infection) to guide decision making. The KSS can generate information sheets for patients, conveyed by the clinicians during consultations. The primary outcome is the practice-level rate of antibiotic prescribing (per 1000 patients) with secondary safety outcomes. The data from practices participating in the trial and the dashboard infrastructure will be held within regional shared care record systems of the National Health Service in the UK.

Ethics and dissemination

Approved by National Health Service Ethics Committee IRAS 290050. The research results will be published in peer-reviewed journals and also disseminated to participating clinical staff and policy and guideline developers.

Trial registration number

ISRCTN16230629.",,doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?pdf=render; doi:https://doi.org/10.1136/bmjopen-2023-076296 @@ -217,56 +218,56 @@ PMC10464871,https://doi.org/,"A methodology to facilitate critical care research 34697502,https://doi.org/10.1038/s41591-021-01556-7,Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.,"Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, Hunt D, Mei XW, Dixon S, Zaccardi F, Khunti K, Watkinson P, Coupland CAC, Doidge J, Harrison DA, Ravanan R, Sheikh A, Robertson C, Hippisley-Cox J.",,Nature medicine,2021,2021-10-25,Y,,,,"Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.",,doi:https://doi.org/10.1038/s41591-021-01556-7; html:https://europepmc.org/articles/PMC8629105; pdf:https://europepmc.org/articles/PMC8629105?pdf=render 35197114,https://doi.org/10.1186/s41512-022-00120-2,Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform.,"OpenSAFELY Collaborative, Williamson EJ, Tazare J, Bhaskaran K, McDonald HI, Walker AJ, Tomlinson L, Wing K, Bacon S, Bates C, Curtis HJ, Forbes HJ, Minassian C, Morton CE, Nightingale E, Mehrkar A, Evans D, Nicholson BD, Leon DA, Inglesby P, MacKenna B, Davies NG, DeVito NJ, Drysdale H, Cockburn J, Hulme WJ, Morley J, Douglas I, Rentsch CT, Mathur R, Wong A, Schultze A, Croker R, Parry J, Hester F, Harper S, Grieve R, Harrison DA, Steyerberg EW, Eggo RM, Diaz-Ordaz K, Keogh R, Evans SJW, Smeeth L, Goldacre B.",,Diagnostic and prognostic research,2022,2022-02-24,Y,Mortality; Infectious disease; Risk stratification; Statistical methodology; Risk Prediction; Covid-19,,,"

Background

Obtaining accurate estimates of the risk of COVID-19-related death in the general population is challenging in the context of changing levels of circulating infection.

Methods

We propose a modelling approach to predict 28-day COVID-19-related death which explicitly accounts for COVID-19 infection prevalence using a series of sub-studies from new landmark times incorporating time-updating proxy measures of COVID-19 infection prevalence. This was compared with an approach ignoring infection prevalence. The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates, rate of COVID-19-related attendances in emergency care, and rate of suspected COVID-19 cases in primary care. We used data within the TPP SystmOne electronic health record system linked to Office for National Statistics mortality data, using the OpenSAFELY platform, working on behalf of NHS England. Prediction models were developed in case-cohort samples with a 100-day follow-up. Validation was undertaken in 28-day cohorts from the target population. We considered predictive performance (discrimination and calibration) in geographical and temporal subsets of data not used in developing the risk prediction models. Simple models were contrasted to models including a full range of predictors.

Results

Prediction models were developed on 11,972,947 individuals, of whom 7999 experienced COVID-19-related death. All models discriminated well between individuals who did and did not experience the outcome, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92-0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled.

Conclusions

Our proposed models allow absolute risk estimation in the context of changing infection prevalence but predictive performance is sensitive to the proxy for infection prevalence. Simple models can provide excellent discrimination and may simplify implementation of risk prediction tools.",,doi:https://doi.org/10.1186/s41512-022-00120-2; html:https://europepmc.org/articles/PMC8865947; pdf:https://europepmc.org/articles/PMC8865947?pdf=render 35354646,https://doi.org/10.1136/thoraxjnl-2021-218629,Relationship between asthma and severe COVID-19: a national cohort study.,"Dolby T, Nafilyan V, Morgan A, Kallis C, Sheikh A, Quint JK.",,Thorax,2023,2022-03-30,Y,Asthma; Covid-19,,,"

Background

We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19.

Methods

We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included.

Results

Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12-17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic.

Discussion

People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.",,doi:https://doi.org/10.1136/thoraxjnl-2021-218629; html:https://europepmc.org/articles/PMC8983409; pdf:https://europepmc.org/articles/PMC8983409?pdf=render; pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/03/29/thoraxjnl-2021-218629.full.pdf -36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"

Objectives

To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.

Design

Retrospective assessment of routinely collected data from electronic healthcare records.

Setting

Single large urban tertiary care centre.

Participants

All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.

Main outcome measures

Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.

Results

7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.

Conclusions

The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render 34446426,https://doi.org/10.1136/bmj.n1931,Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.,"Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, Zaccardi F, Watkinson P, Shankar-Hari M, Doidge J, Harrison DA, Griffin SJ, Sheikh A, Coupland CAC.",,BMJ (Clinical research ed.),2021,2021-08-26,Y,,,,"

Objective

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

Design

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

Setting

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

Participants

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

Main outcome measures

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

Results

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

Conclusion

Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.",,doi:https://doi.org/10.1136/bmj.n1931; html:https://europepmc.org/articles/PMC8388189; pdf:https://europepmc.org/articles/PMC8388189?pdf=render +36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"

Objectives

To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.

Design

Retrospective assessment of routinely collected data from electronic healthcare records.

Setting

Single large urban tertiary care centre.

Participants

All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.

Main outcome measures

Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.

Results

7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.

Conclusions

The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render 31566668,https://doi.org/10.1093/ageing/afz110,External validation of the electronic Frailty Index using the population of Wales within the Secure Anonymised Information Linkage Databank. ,"Hollinghurst J, Fry R, Akbari A, Clegg A, Lyons RA, Watkins A, Rodgers SE.",,Age and ageing,2019,2019-11-01,Y,,Improving Public Health,,"frailty has major implications for health and social care services internationally. The development, validation and national implementation of the electronic Frailty Index (eFI) using routine primary care data has enabled change in the care of older people living with frailty in England. to externally validate the eFI in Wales and assess new frailty-related outcomes. retrospective cohort study using the Secure Anonymised Information Linkage (SAIL) Databank, comprising 469,000 people aged 65-95, registered with a SAIL contributing general practice on 1 January 2010. four categories (fit; mild; moderate and severe) of frailty were constructed using recognised cut points from the eFI. We calculated adjusted hazard ratios (HRs) from Cox regression models for validation of existing outcomes: 1-, 3- and 5-year mortality, hospitalisation, and care home admission for validation. We also analysed, as novel outcomes, 1-year mortality following hospitalisation and frailty transition times. HR trends for the validation outcomes in SAIL followed the original results from ResearchOne and THIN databases. Relative to the fit category, adjusted HRs in SAIL (95% CI) for 1-year mortality following hospitalisation were 1.05 (95% CI 1.03-1.08) for mild frailty, 1.24 (95% CI 1.21-1.28) for moderate frailty and 1.51 (95% CI 1.45-1.57) for severe frailty. The median time (lower and upper quartile) between frailty categories was 2,165 days (lower and upper quartiles: 1,510 and 2,831) from fit to mild, 1,155 days (lower and upper quartiles: 756 and 1,610) from mild to moderate and 898 days (lower and upper quartiles: 584 and 1,275) from moderate to severe. further validation of the eFI showed robust predictive validity and utility for new outcomes.",,doi:https://doi.org/10.1093/ageing/afz110; html:https://europepmc.org/articles/PMC6814149; pdf:https://europepmc.org/articles/PMC6814149?pdf=render -37181393,https://doi.org/10.1016/j.jacasi.2022.12.006,Ambient Temperature and Myocardial Infarction: Who Is at Risk?,"Lowry MTH, Mills NL, Kimenai DM.",,JACC. Asia,2023,2023-03-14,Y,Myocardial infarction; Ambient temperature; risk factors,,,,,doi:https://doi.org/10.1016/j.jacasi.2022.12.006; html:https://europepmc.org/articles/PMC10167505; pdf:https://europepmc.org/articles/PMC10167505?pdf=render 37387161,https://doi.org/10.1093/bioinformatics/btad240,SynBa: improved estimation of drug combination synergies with uncertainty quantification.,"Zhang H, Ek CH, Rattray M, Milo M.",,"Bioinformatics (Oxford, England)",2023,2023-06-01,Y,,,,"

Motivation

There exists a range of different quantification frameworks to estimate the synergistic effect of drug combinations. The diversity and disagreement in estimates make it challenging to determine which combinations from a large drug screening should be proceeded with. Furthermore, the lack of accurate uncertainty quantification for those estimates precludes the choice of optimal drug combinations based on the most favourable synergistic effect.

Results

In this work, we propose SynBa, a flexible Bayesian approach to estimate the uncertainty of the synergistic efficacy and potency of drug combinations, so that actionable decisions can be derived from the model outputs. The actionability is enabled by incorporating the Hill equation into SynBa, so that the parameters representing the potency and the efficacy can be preserved. Existing knowledge may be conveniently inserted due to the flexibility of the prior, as shown by the empirical Beta prior defined for the normalized maximal inhibition. Through experiments on large combination screenings and comparison against benchmark methods, we show that SynBa provides improved accuracy of dose-response predictions and better-calibrated uncertainty estimation for the parameters and the predictions.

Availability and implementation

The code for SynBa is available at https://github.com/HaotingZhang1/SynBa. The datasets are publicly available (DOI of DREAM: 10.7303/syn4231880; DOI of the NCI-ALMANAC subset: 10.5281/zenodo.4135059).",,doi:https://doi.org/10.1093/bioinformatics/btad240; html:https://europepmc.org/articles/PMC10311304; pdf:https://europepmc.org/articles/PMC10311304?pdf=render +37181393,https://doi.org/10.1016/j.jacasi.2022.12.006,Ambient Temperature and Myocardial Infarction: Who Is at Risk?,"Lowry MTH, Mills NL, Kimenai DM.",,JACC. Asia,2023,2023-03-14,Y,Myocardial infarction; Ambient temperature; risk factors,,,,,doi:https://doi.org/10.1016/j.jacasi.2022.12.006; html:https://europepmc.org/articles/PMC10167505; pdf:https://europepmc.org/articles/PMC10167505?pdf=render 34304048,https://doi.org/10.1016/j.ebiom.2021.103485,Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,EBioMedicine,2021,2021-07-23,Y,,,,"Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render 34385524,https://doi.org/10.1038/s41598-021-95802-0,Multimorbidity prediction using link prediction.,"Aziz F, Cardoso VR, Bravo-Merodio L, Russ D, Pendleton SC, Williams JA, Acharjee A, Gkoutos GV.",,Scientific reports,2021,2021-08-12,Y,,,,"Multimorbidity, frequently associated with aging, can be operationally defined as the presence of two or more chronic conditions. Predicting the likelihood of a patient with multimorbidity to develop a further particular disease in the future is one of the key challenges in multimorbidity research. In this paper we are using a network-based approach to analyze multimorbidity data and develop methods for predicting diseases that a patient is likely to develop. The multimorbidity data is represented using a temporal bipartite network whose nodes represent patients and diseases and a link between these nodes indicates that the patient has been diagnosed with the disease. Disease prediction then is reduced to a problem of predicting those missing links in the network that are likely to appear in the future. We develop a novel link prediction method for static bipartite network and validate the performance of the method on benchmark datasets. By using a probabilistic framework, we then report on the development of a method for predicting future links in the network, where links are labelled with a time-stamp. We apply the proposed method to three different multimorbidity datasets and report its performance measured by different performance metrics including AUC, Precision, Recall, and F-Score.",,doi:https://doi.org/10.1038/s41598-021-95802-0; html:https://europepmc.org/articles/PMC8360941; pdf:https://europepmc.org/articles/PMC8360941?pdf=render 34977922,https://doi.org/10.1093/ije/dyab243,Cohort Profile: The COVID-19 in Pregnancy in Scotland (COPS) dynamic cohort of pregnant women to assess effects of viral and vaccine exposures on pregnancy.,"Stock SJ, Carruthers J, Denny C, Donaghy J, Goulding A, Hopcroft LEM, Hopkins L, Mulholland R, Agrawal U, Auyeung B, Katikireddi SV, McCowan C, Murray J, Robertson C, Sheikh A, Shi T, Simpson CR, Vasileiou E, Wood R.",,International journal of epidemiology,2022,2022-10-01,Y,,,,,,doi:https://doi.org/10.1093/ije/dyab243; html:https://europepmc.org/articles/PMC9557859; pdf:https://europepmc.org/articles/PMC9557859?pdf=render 35165107,https://doi.org/10.1136/bmjopen-2021-050062,"Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.","Vasileiou E, Shi T, Kerr S, Robertson C, Joy M, Tsang R, McGagh D, Williams J, Hobbs R, de Lusignan S, de Lusignan S, Bradley D, OReilly D, Murphy S, Chuter A, Beggs J, Ford D, Orton C, Akbari A, Bedston S, Davies G, Griffiths LJ, Griffiths R, Lowthian E, Lyons J, Lyons RA, North L, Perry M, Torabi F, Pickett J, McMenamin J, McCowan C, Agrawal U, Wood R, Stock SJ, Moore E, Henery P, Simpson CR, Sheikh A.",,BMJ open,2022,2022-02-14,Y,epidemiology; Public Health; Respiratory Infections; Covid-19,,,"

Introduction

The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods and analysis

We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics and dissemination

We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render 35910710,https://doi.org/10.1093/rap/rkac056,Real-world use of an etanercept biosimilar including selective versus automatic substitution in inflammatory arthritis patients: a UK-based electronic health records study.,"Cooksey R, Brophy S, Kennedy J, Seaborne M, Choy E.",,Rheumatology advances in practice,2022,2022-07-27,Y,RA; As; PSA; Etanercept; Biosimilars,,,"

Objective

Biosimilars are approved as an alternative treatment to their originators. We compared the clinical outcomes of etanercept (ETN) biosimilar compared with ETN originator in real-world practice, from two local health boards in Wales with different policies on switching: automatic vs selective.

Methods

Data from the Secure Anonymised Information Linkage (SAIL) databank in Wales were used to create a retrospective cohort study using linked primary and secondary care data. Patients aged ≥18 years with diagnosis codes for RA, PsA or AS were included. Outcomes included treatment failure and DAS-28 score (for RA). The local health board with a policy of automatic switching (i.e. clinician/nurse involvement not mandated) is labelled as automatic switch area, and the other, which required clinician/nurse supervision, as selective switch.

Results

Of 8925 individuals with inflammatory arthritis, 13.3% (365) received ETN biosimilar and 31.5% (863) ETN originator. The treatment discontinuation rate was similar for ETN biosimilar and originator by Kaplan-Meier analysis. More biosimilar failure patients were treated in the automatic switch area (15 vs 4.8%). In the automatic switch area, 28.8% (75 of 260) of patients switched automatically from ETN originator to biosimilar compared with 10.5% (11 of 105) in the selective switch area. ETN biosimilar reduced DAS-28 by 1.6 ± 1.8 in the selective switch area vs 0.4 ± 0.6 in the automatic switch area.

Conclusion

The ETN biosimilar was well tolerated. Fewer people were switched using selective policy, but this was associated with lower failure rates. Automatic switch policy led to more patients being switched and did not lead to significant worsening of disease.",,doi:https://doi.org/10.1093/rap/rkac056; html:https://europepmc.org/articles/PMC9336562; pdf:https://europepmc.org/articles/PMC9336562?pdf=render 37363797,https://doi.org/10.1016/j.lanepe.2023.100653,Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Lancet regional health. Europe,2023,2023-05-16,Y,Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic,,,"

Background

The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.

Methods

With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.

Findings

Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).

Interpretation

An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.

Funding

This work was supported by Health Data Research UK and by National Institute for Health Research.",,doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render -37363796,https://doi.org/10.1016/j.lanepe.2023.100636,Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study.,"OpenSAFELY Collaborative, Parker EPK, Horne EMF, Hulme WJ, Tazare J, Zheng B, Carr EJ, Loud F, Lyon S, Mahalingasivam V, MacKenna B, Mehrkar A, Scanlon M, Santhakumaran S, Steenkamp R, Goldacre B, Sterne JAC, Nitsch D, Tomlinson LA, LH&W NCS (or CONVALESCENCE) Collaborative.",,The Lancet regional health. Europe,2023,2023-05-03,Y,Vaccination; Effectiveness; Chronic Kidney Disease; Nhs England; Covid-19; Sars-cov-2,,,"

Background

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England.

Methods

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

Findings

After two doses, incidence during the Delta wave was higher in AZ-AZ (n = 257,580) than BNT-BNT recipients (n = 169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n = 220,330) and BNT-BNT-BNT recipients (n = 157,065) for any outcome during a period of Omicron dominance.

Interpretation

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

Funding

National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2023.100636; html:https://europepmc.org/articles/PMC10155829; pdf:https://europepmc.org/articles/PMC10155829?pdf=render 32016358,https://doi.org/10.1093/ecco-jcc/jjaa021,"A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways.","Quraishi MN, Acharjee A, Beggs AD, Horniblow R, Tselepis C, Gkoutos G, Ghosh S, Rossiter AE, Loman N, van Schaik W, Withers D, Walters JRF, Hirschfield GM, Iqbal TH.",,Journal of Crohn's & colitis,2020,2020-07-01,Y,Bioinformatics; Colitis; Dysbiosis; Autoimmune Liver Disease,,,"

Background

Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data.

Methods

Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration.

Results

The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD.

Conclusions

Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.",,doi:https://doi.org/10.1093/ecco-jcc/jjaa021; html:https://europepmc.org/articles/PMC7392170; pdf:https://europepmc.org/articles/PMC7392170?pdf=render -34445233,https://doi.org/10.3390/ijms22168527,The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers. ,"Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.",,International journal of molecular sciences,2021,2021-08-08,Y,,,,"MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.",,doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render +37363796,https://doi.org/10.1016/j.lanepe.2023.100636,Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study.,"OpenSAFELY Collaborative, Parker EPK, Horne EMF, Hulme WJ, Tazare J, Zheng B, Carr EJ, Loud F, Lyon S, Mahalingasivam V, MacKenna B, Mehrkar A, Scanlon M, Santhakumaran S, Steenkamp R, Goldacre B, Sterne JAC, Nitsch D, Tomlinson LA, LH&W NCS (or CONVALESCENCE) Collaborative.",,The Lancet regional health. Europe,2023,2023-05-03,Y,Vaccination; Effectiveness; Chronic Kidney Disease; Nhs England; Covid-19; Sars-cov-2,,,"

Background

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England.

Methods

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

Findings

After two doses, incidence during the Delta wave was higher in AZ-AZ (n = 257,580) than BNT-BNT recipients (n = 169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n = 220,330) and BNT-BNT-BNT recipients (n = 157,065) for any outcome during a period of Omicron dominance.

Interpretation

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

Funding

National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2023.100636; html:https://europepmc.org/articles/PMC10155829; pdf:https://europepmc.org/articles/PMC10155829?pdf=render 36941845,https://doi.org/10.1016/j.xkme.2023.100613,"Cognitive Impairment, Frailty, and Adverse Outcomes Among Prevalent Hemodialysis Recipients: Results From a Large Prospective Cohort Study in the United Kingdom.","Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,Kidney medicine,2023,2023-02-09,Y,Mortality; Frailty; Dementia; Cognitive impairment; epidemiology; hemodialysis; Hospitalization; End-stage Kidney Disease,,,"

Rationale & objective

Frailty and cognitive impairment are common in hemodialysis recipients and have been associated with high mortality. There is considerable heterogeneity in frailty reporting, with little comparison between commonly used frailty tools and little exploration of the interplay between cognition and frailty. The aims were to explore the relationship between frailty scores and cognition and their associations with hospitalization and mortality.

Study design

Prospective cohort study.

Setting & population

Prevalent hemodialysis recipients linked to national datasets for hospitalization and mortality.

Predictors

Montreal Cognitive Assessment (MoCA), Frailty Phenotype, Frailty Index (FI), Edmonton Frailty Scale, and Clinical Frailty Scale (CFS) were performed at baseline. Cognitive impairment was defined as MoCA scores of <26, or <21 in dexterity impairment, <18 in visual impairment.

Outcomes

Mortality, hospitalization.

Analytical approach

Cox proportional hazards model for mortality, censored for end of follow-up. Negative binomial regression for admission rates, censored for death/end of follow-up.

Results

In total, 448 participants were recruited with valid MoCAs and followed up for a median of 685 days. There were 103 (23%) deaths and 1,120 admissions of at least one night. Cognitive impairment was identified in 346 (77.2%) participants. Increasing frailty by all definitions was associated with poorer cognition. Cognition was not associated with mortality (HR, 0.99; 95% CI, 0.95-1.03; P = 0.41) or hospitalization (IRR, 1.01; 95% CI, 0.99-1.04; P = 0.39) on multivariable analyses. There were interactions between MoCA scores and increasing frailty by FI (P = 0.002) and Clinical Frailty Scale (P = 0.005); admissions were highest when both MoCA and frailty scores were high, and when both scores were low.

Limitations

As frailty is a dynamic state, a single cross-sectional assessment may not accurately reflect its year-to-year variability. In addition, these findings are in maintenance dialysis and may not be transferable to incident hemodialysis. There were small variations in application of frailty tool criteria from other studies, which may have influenced the results.

Conclusions

Cognitive impairment is highly prevalent in this hemodialysis cohort. The interaction between cognition and frailty on rates of admission suggests the MoCA offers value in identifying higher risk hemodialysis populations with both high and low degrees of frailty.",,doi:https://doi.org/10.1016/j.xkme.2023.100613; html:https://europepmc.org/articles/PMC10024232; pdf:https://europepmc.org/articles/PMC10024232?pdf=render +34445233,https://doi.org/10.3390/ijms22168527,The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers. ,"Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.",,International journal of molecular sciences,2021,2021-08-08,Y,,,,"MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.",,doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render 35473737,https://doi.org/10.1136/bmjopen-2021-060413,"Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).","Haroon S, Nirantharakumar K, Hughes SE, Subramanian A, Aiyegbusi OL, Davies EH, Myles P, Williams T, Turner G, Chandan JS, McMullan C, Lord J, Wraith DC, McGee K, Denniston AK, Taverner T, Jackson LJ, Sapey E, Gkoutos G, Gokhale K, Leggett E, Iles C, Frost C, McNamara G, Bamford A, Marshall T, Zemedikun DT, Price G, Marwaha S, Simms-Williams N, Brown K, Walker A, Jones K, Matthews K, Camaradou J, Saint-Cricq M, Kumar S, Alder Y, Stanton DE, Agyen L, Baber M, Blaize H, Calvert M.",,BMJ open,2022,2022-04-26,Y,Therapeutics; immunology; Public Health; Covid-19,,,"

Introduction

Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.

Methods and analysis

A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.

Ethics and dissemination

Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.

Trial registration number

1567490.",,doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render 32043136,https://doi.org/10.1093/ageing/afaa018,New Horizons in the use of routine data for ageing research.,"Todd OM, Burton JK, Dodds RM, Hollinghurst J, Lyons RA, Quinn TJ, Schneider A, Walesby KE, Wilkinson C, Conroy S, Gale CP, Hall M, Walters K, Clegg AP.",,Age and ageing,2020,2020-08-01,Y,Ageing; Data Linkage; Older People; Health Informatics; Electronic Health Records; Big Data,Improving Public Health,,"The past three decades have seen a steady increase in the availability of routinely collected health and social care data and the processing power to analyse it. These developments represent a major opportunity for ageing research, especially with the integration of different datasets across traditional boundaries of health and social care, for prognostic research and novel evaluations of interventions with representative populations of older people. However, there are considerable challenges in using routine data at the level of coding, data analysis and in the application of findings to everyday care. New Horizons in applying routine data to investigate novel questions in ageing research require a collaborative approach between clinicians, data scientists, biostatisticians, epidemiologists and trial methodologists. This requires building capacity for the next generation of research leaders in this important area. There is a need to develop consensus code lists and standardised, validated algorithms for common conditions and outcomes that are relevant for older people to maximise the potential of routine data research in this group. Lastly, we must help drive the application of routine data to improve the care of older people, through the development of novel methods for evaluation of interventions using routine data infrastructure. We believe that harnessing routine data can help address knowledge gaps for older people living with multiple conditions and frailty, and design interventions and pathways of care to address the complex health issues we face in caring for older people.","This article looks at new horizons in the use of routine data for ageing research. This includes prognostic research, clinical trials, and service evaluations. The authors highlight the need for multidisciplinary collaboration. They identify three key areas where the application of routine data has major benefits for research in ageing - prediction (developing prediction tools to identify levels of future risk of outcomes thereby helping in decision making), clinical trials (routine data can help extend participation in clinical trials), and service evaluation (understanding performace of clinical services by measuring outcomes in routine data).",doi:https://doi.org/10.1093/ageing/afaa018; html:https://europepmc.org/articles/PMC7444666; pdf:https://europepmc.org/articles/PMC7444666?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/49/5/716/33676968/afaa018.pdf 34879829,https://doi.org/10.1186/s12911-021-01693-6,Identifying and evaluating clinical subtypes of Alzheimer's disease in care electronic health records using unsupervised machine learning.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,BMC medical informatics and decision making,2021,2021-12-08,Y,Alzheimer's disease; Clustering; Subtyping; Ehr; K-means,,,"

Background

Alzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable.

Methods

We identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets.

Results

We identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters.

Conclusion

Each clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR.",,doi:https://doi.org/10.1186/s12911-021-01693-6; html:https://europepmc.org/articles/PMC8653614; pdf:https://europepmc.org/articles/PMC8653614?pdf=render 36460578,https://doi.org/10.1016/s2589-7500(22)00187-x,Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study.,"Kuan V, Denaxas S, Patalay P, Nitsch D, Mathur R, Gonzalez-Izquierdo A, Sofat R, Partridge L, Roberts A, Wong ICK, Hingorani M, Chaturvedi N, Hemingway H, Hingorani AD, Multimorbidity Mechanism and Therapeutic Research Collaborative (MMTRC).",,The Lancet. Digital health,2023,2022-11-29,N,,,,"

Background

Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population.

Methods

In this population-based study, we examined multimorbidity and comorbidity patterns stratified by ethnicity or race, sex, and age for 308 health conditions using electronic health records from individuals included on the Clinical Practice Research Datalink linked with the Hospital Episode Statistics admitted patient care dataset in England. We included individuals who were older than 1 year and who had been registered for at least 1 year in a participating general practice during the study period (between April 1, 2010, and March 31, 2015). We identified the most common combinations of conditions and comorbidities for index conditions. We defined comorbidity as the accumulation of additional conditions to an index condition over an individual's lifetime. We used network analysis to identify conditions that co-occurred more often than expected by chance. We developed online interactive tools to explore multimorbidity and comorbidity patterns overall and by subgroup based on ethnicity, sex, and age.

Findings

We collected data for 3 872 451 eligible patients, of whom 1 955 700 (50·5%) were women and girls, 1 916 751 (49·5%) were men and boys, 2 666 234 (68·9%) were White, 155 435 (4·0%) were south Asian, and 98 815 (2·6%) were Black. We found that a higher proportion of boys aged 1-9 years (132 506 [47·8%] of 277 158) had two or more diagnosed conditions than did girls in the same age group (106 982 [40·3%] of 265 179), but more women and girls were diagnosed with multimorbidity than were boys aged 10 years and older and men (1 361 232 [80·5%] of 1 690 521 vs 1 161 308 [70·8%] of 1 639 593). White individuals (2 097 536 [78·7%] of 2 666 234) were more likely to be diagnosed with two or more conditions than were Black (59 339 [60·1%] of 98 815) or south Asian individuals (93 617 [60·2%] of 155 435). Depression commonly co-occurred with anxiety, migraine, obesity, atopic conditions, deafness, soft-tissue disorders, and gastrointestinal disorders across all subgroups. Heart failure often co-occurred with hypertension, atrial fibrillation, osteoarthritis, stable angina, myocardial infarction, chronic kidney disease, type 2 diabetes, and chronic obstructive pulmonary disease. Spinal fractures were most strongly non-randomly associated with malignancy in Black individuals, but with osteoporosis in White individuals. Hypertension was most strongly associated with kidney disorders in those aged 20-29 years, but with dyslipidaemia, obesity, and type 2 diabetes in individuals aged 40 years and older. Breast cancer was associated with different comorbidities in individuals from different ethnic groups. Asthma was associated with different comorbidities between males and females. Bipolar disorder was associated with different comorbidities in younger age groups compared with older age groups.

Interpretation

Our findings and interactive online tools are a resource for: patients and their clinicians, to prevent and detect comorbid conditions; research funders and policy makers, to redesign service provision, training priorities, and guideline development; and biomedical researchers and manufacturers of medicines, to provide leads for research into common or sequential pathways of disease and inform the design of clinical trials.

Funding

UK Research and Innovation, Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, Wellcome Trust, British Heart Foundation, and The Alan Turing Institute.",,doi:https://doi.org/10.1016/S2589-7500(22)00187-X 33228632,https://doi.org/10.1186/s12920-020-00826-6,A random forest based biomarker discovery and power analysis framework for diagnostics research.,"Acharjee A, Larkman J, Xu Y, Cardoso VR, Gkoutos GV.",,BMC medical genomics,2020,2020-11-23,Y,Biomarker; Feature Selection; Random Forest; Power Study,,,"

Background

Biomarker identification is one of the major and important goal of functional genomics and translational medicine studies. Large scale -omics data are increasingly being accumulated and can provide vital means for the identification of biomarkers for the early diagnosis of complex disease and/or for advanced patient/diseases stratification. These tasks are clearly interlinked, and it is essential that an unbiased and stable methodology is applied in order to address them. Although, recently, many, primarily machine learning based, biomarker identification approaches have been developed, the exploration of potential associations between biomarker identification and the design of future experiments remains a challenge.

Methods

In this study, using both simulated and published experimentally derived datasets, we assessed the performance of several state-of-the-art Random Forest (RF) based decision approaches, namely the Boruta method, the permutation based feature selection without correction method, the permutation based feature selection with correction method, and the backward elimination based feature selection method. Moreover, we conducted a power analysis to estimate the number of samples required for potential future studies.

Results

We present a number of different RF based stable feature selection methods and compare their performances using simulated, as well as published, experimentally derived, datasets. Across all of the scenarios considered, we found the Boruta method to be the most stable methodology, whilst the Permutation (Raw) approach offered the largest number of relevant features, when allowed to stabilise over a number of iterations. Finally, we developed and made available a web interface ( https://joelarkman.shinyapps.io/PowerTools/ ) to streamline power calculations thereby aiding the design of potential future studies within a translational medicine context.

Conclusions

We developed a RF-based biomarker discovery framework and provide a web interface for our framework, termed PowerTools, that caters the design of appropriate and cost-effective subsequent future omics study.",,doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render 37182748,https://doi.org/10.1016/j.jinf.2023.05.010,The impact of COVID-19 on antibiotic prescribing in primary care in England: Evaluation and risk prediction of appropriateness of type and repeat prescribing.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Journal of infection,2023,2023-05-12,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"

Background

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

Methods

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

Results

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

Conclusions

Our study found no evidence of changes in level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.",,doi:https://doi.org/10.1016/j.jinf.2023.05.010; html:https://europepmc.org/articles/PMC10176893; pdf:https://europepmc.org/articles/PMC10176893?pdf=render; doi:https://doi.org/10.1016/j.jinf.2023.05.010 -37558806,https://doi.org/10.1038/s41598-023-40215-4,"Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.","Simonyte S, Grabauskyte I, Macijauskiene J, Lesauskaite V, Lesauskaite V, Kvaal KS, Stewart R.",,Scientific reports,2023,2023-08-09,Y,,,,"Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.",,doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render 35226680,https://doi.org/10.1371/journal.pone.0264023,"COVID-19 mitigation measures in primary schools and association with infection and school staff wellbeing: An observational survey linked with routine data in Wales, UK.","Marchant E, Griffiths L, Crick T, Fry R, Hollinghurst J, James M, Cowley L, Abbasizanjani H, Torabi F, Thompson DA, Kennedy J, Akbari A, Gravenor MB, Lyons RA, Brophy S.",,PloS one,2022,2022-02-28,Y,,,,"

Introduction

School-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, two metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation measures and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK.

Methods

A school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank.

Results

Responses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement two metre social distancing from pupils. We did not find evidence that maintaining a two metre distance was associated with lower rates of COVID-19 in the school.

Conclusions

Implementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, two metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.",,doi:https://doi.org/10.1371/journal.pone.0264023; html:https://europepmc.org/articles/PMC8884508; pdf:https://europepmc.org/articles/PMC8884508?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264023&type=printable +37558806,https://doi.org/10.1038/s41598-023-40215-4,"Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.","Simonyte S, Grabauskyte I, Macijauskiene J, Lesauskaite V, Lesauskaite V, Kvaal KS, Stewart R.",,Scientific reports,2023,2023-08-09,Y,,,,"Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.",,doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render 37171130,https://doi.org/10.1093/gigascience/giad030,Strategies and techniques for quality control and semantic enrichment with multimodal data: a case study in colorectal cancer with eHDPrep.,"Toner TM, Pancholi R, Miller P, Forster T, Coleman HG, Overton IM.",,GigaScience,2022,2022-12-01,Y,Quality control; Bioinformatics; Data integration; Quality assessment; Colorectal Cancer; Medical Informatics; Ontology; Health Data; Semantic Enrichment,,,"

Background

Integration of data from multiple domains can greatly enhance the quality and applicability of knowledge generated in analysis workflows. However, working with health data is challenging, requiring careful preparation in order to support meaningful interpretation and robust results. Ontologies encapsulate relationships between variables that can enrich the semantic content of health datasets to enhance interpretability and inform downstream analyses.

Findings

We developed an R package for electronic health data preparation, ""eHDPrep,"" demonstrated upon a multimodal colorectal cancer dataset (661 patients, 155 variables; Colo-661); a further demonstrator is taken from The Cancer Genome Atlas (459 patients, 94 variables; TCGA-COAD). eHDPrep offers user-friendly methods for quality control, including internal consistency checking and redundancy removal with information-theoretic variable merging. Semantic enrichment functionality is provided, enabling generation of new informative ""meta-variables"" according to ontological common ancestry between variables, demonstrated with SNOMED CT and the Gene Ontology in the current study. eHDPrep also facilitates numerical encoding, variable extraction from free text, completeness analysis, and user review of modifications to the dataset.

Conclusions

eHDPrep provides effective tools to assess and enhance data quality, laying the foundation for robust performance and interpretability in downstream analyses. Application to multimodal colorectal cancer datasets resulted in improved data quality, structuring, and robust encoding, as well as enhanced semantic information. We make eHDPrep available as an R package from CRAN (https://cran.r-project.org/package = eHDPrep) and GitHub (https://github.com/overton-group/eHDPrep).",,doi:https://doi.org/10.1093/gigascience/giad030; html:https://europepmc.org/articles/PMC10176503; pdf:https://europepmc.org/articles/PMC10176503?pdf=render 37046692,https://doi.org/10.3390/cancers15072031,"Breast, Prostate, Colorectal, and Lung Cancer Incidence and Risk Factors in Women Who Have Sex with Women and Men Who Have Sex with Men: A Cross-Sectional and Longitudinal Analysis Using UK Biobank.","Underwood S, Lyratzopoulos G, Saunders CL.",,Cancers,2023,2023-03-29,Y,Inequalities; Cancer Incidence; Cancer Risk; Cancer Epidemiology; Sexual Minority Health,,,"

Background

There is limited evidence about cancer incidence for lesbian, gay and bisexual women and men, although the prevalence of cancer risk factors may be higher.

Aim

To describe cancer incidence for four common cancers (breast, lung, colorectal and prostate).

Methods

This project used UK Biobank participant data. We explored risk factor prevalence (age, deprivation, ethnicity, smoking, alcohol intake, obesity, parity, and sexual history), and calculated cancer risk, for six groups defined based on sexual history; women who have sex exclusively with men (WSEM), or women (WSEW), women who have sex with men and women (WSWM); men who have sex exclusively with women (MSEW), or men (MSEM), and men who have sex with women and men (MSWM).

Results

WSEW, WSWM, MSEM, and MSMW were younger, more likely to smoke, and to live in more deprived neighbourhoods. We found no evidence of an association between sexual history and breast, colorectal, or prostate cancer in age-adjusted models. Lung cancer incidence was higher for WSWM compared with WSEM, HR (95%CI) 1.78 (1.28-2.48), p = 0.0005, and MSWM compared with MSEW, 1.43 (1.03-1.99), p = 0.031; after adjustment for smoking, this difference was no longer significant.

Conclusions

Sexual minority groups have a higher risk for lung cancer, due to greater exposure to smoking.",,doi:https://doi.org/10.3390/cancers15072031; html:https://europepmc.org/articles/PMC10093616; pdf:https://europepmc.org/articles/PMC10093616?pdf=render -36944118,https://doi.org/10.2337/dc22-1238,Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.,"Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",,Diabetes care,2023,2023-05-01,Y,,,,"

Objective

To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.

Research design and methods

A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.

Results

Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).

Conclusions

Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",,doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render 32634370,https://doi.org/10.1098/rsob.200121,Core regulatory circuitries in defining cancer cell identity across the malignant spectrum.,"Jahangiri L, Tsaprouni L, Trigg RM, Williams JA, Gkoutos GV, Turner SD, Pereira J.",,Open biology,2020,2020-07-08,Y,Cell Identity; Super-enhancers; Core Regulatory Circuitry; Liquid And Solid Cancers,,,"Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permissive H3K27ac chromatin marks. These super-enhancers are largely associated with BET proteins, including BRD4, that influence higher-order chromatin structure. The orchestration of these events triggers accessibility of RNA polymerase machinery and the imposition of lineage-specific gene expression. In cancers, CRCs drive cell identity by superimposing developmental programmes on a background of genetic alterations. Further, the establishment and maintenance of oncogenic states are reliant on CRCs that drive factors involved in tumour development. Hence, the molecular dissection of CRC components driving cell identity and cancer state can contribute to elucidating mechanisms of diversion from pre-determined developmental programmes and highlight cancer dependencies. These insights can provide valuable opportunities for identifying and re-purposing drug targets. In this article, we review the current understanding of CRCs across solid and liquid malignancies and avenues of investigation for drug development efforts. We also review techniques used to understand CRCs and elaborate the indication of discussed CRC transcription factors in the wider context of cancer CRC models.",,doi:https://doi.org/10.1098/rsob.200121; html:https://europepmc.org/articles/PMC7574545; pdf:https://europepmc.org/articles/PMC7574545?pdf=render +36944118,https://doi.org/10.2337/dc22-1238,Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.,"Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",,Diabetes care,2023,2023-05-01,Y,,,,"

Objective

To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.

Research design and methods

A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.

Results

Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).

Conclusions

Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",,doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render 36530697,https://doi.org/10.3389/fpubh.2022.1035415,Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.,"Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.",,Frontiers in public health,2022,2022-12-02,Y,Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity,,,"

Background

Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.

Methods

Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (μg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.

Results

Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)].

Conclusions

This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.",,doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render 34829865,https://doi.org/10.3390/biomedicines9111636,Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers. ,"Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.",,Biomedicines,2021,2021-11-07,Y,,,,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.",,doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render 33683514,https://doi.org/10.1007/s10237-021-01437-5,A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations.,"Coccarelli A, Carson JM, Aggarwal A, Pant S.",,Biomechanics and modeling in mechanobiology,2021,2021-03-08,Y,Pulse wave velocity; Common carotid artery; Hyperelasticity; Tube Law; One-dimensional Blood Flow Modelling; Axial Stretching,,,"We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel-Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol's multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system's haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.",,doi:https://doi.org/10.1007/s10237-021-01437-5; html:https://europepmc.org/articles/PMC8298378; pdf:https://europepmc.org/articles/PMC8298378?pdf=render 30381314,https://doi.org/10.1136/bmjopen-2018-026290,Study protocol for investigating the impact of community home modification services on hospital utilisation for fall injuries: a controlled longitudinal study using data linkage. ,"Hollinghurst J, Akbari A, Fry R, Watkins A, Berridge D, Clegg A, Hillcoat-Nalletamby S, Williams N, Lyons R, Mizen A, Walters A, Johnson R, Rodgers S.",,BMJ open,2018,2018-10-30,Y,,Improving Public Health,,"This study will evaluate the effectiveness of home adaptations, both in preventing hospital admissions due to falls for older people, and improving timely discharge. Results will provide evidence for services at the interface between health and social care, informing policies seeking to promote healthy ageing through prudent healthcare and fall prevention. All individuals living in Wales, UK, aged 60 years and over, will be included in the study using anonymised linked data from the Secure Anonymised Information Linkage Databank. We will use a national database of home modifications implemented by the charity organisation Care & Repair Cymru (C&R) from 2009 to 2017 to define an intervention cohort. We will use the electronic Frailty Index to assign individual levels of frailty (fit, mild, moderate or severe) and use these to create a comparator group (non-C&R) of people who have not received a C&R intervention. Coprimary outcomes will be quarterly numbers of emergency hospital admissions attributed to falls at home, and the associated length of stay. Secondary outcomes include the time in moving to a care home following a fall, and the indicative financial costs of care for individuals who had a fall. We will use appropriate multilevel generalised linear models to analyse the number of hospital admissions related to falls. We will use Cox proportional hazard models to compare the length of stay for fall-related hospital admissions and the time in moving to a care home between the C&R and non-C&R cohorts. We will assess the impact per frailty group, correct for population migration and adjust for confounding variables. Indicative costs will be calculated using financial codes for individual-level hospital stays. Results will provide evidence for services at the interface between health and social care, informing policies seeking to promote healthy ageing through prudent healthcare and prevention. Information governance requirements for the use of record-linked data have been approved and only anonymised data will be used in our analysis. Our results will be submitted for publication in peer-reviewed journals. We will also work with lay members and the knowledge transfer team at Swansea University to create communication and dissemination materials on key findings.",,doi:https://doi.org/10.1136/bmjopen-2018-026290; html:https://europepmc.org/articles/PMC6224723; pdf:https://europepmc.org/articles/PMC6224723?pdf=render -36701357,https://doi.org/10.1371/journal.pone.0280943,Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.,"Cooper E, Lound A, Atchison CJ, Whitaker M, Eccles C, Cooke GS, Elliott P, Ward H.",,PloS one,2023,2023-01-26,Y,,,,"

Background

Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.

Methods

People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.

Results

We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.

Conclusion

This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.",,doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render 34108714,https://doi.org/10.1038/s41591-021-01408-4,"First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.","Simpson CR, Shi T, Vasileiou E, Katikireddi SV, Kerr S, Moore E, McCowan C, Agrawal U, Shah SA, Ritchie LD, Murray J, Pan J, Bradley DT, Stock SJ, Wood R, Chuter A, Beggs J, Stagg HR, Joy M, Tsang RSM, de Lusignan S, Hobbs R, Lyons RA, Torabi F, Bedston S, O'Leary M, Akbari A, McMenamin J, Robertson C, Sheikh A.",,Nature medicine,2021,2021-06-09,Y,,,,"Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.",,doi:https://doi.org/10.1038/s41591-021-01408-4; html:https://europepmc.org/articles/PMC8282499; pdf:https://europepmc.org/articles/PMC8282499?pdf=render; pdf:https://www.nature.com/articles/s41591-021-01408-4.pdf +36701357,https://doi.org/10.1371/journal.pone.0280943,Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.,"Cooper E, Lound A, Atchison CJ, Whitaker M, Eccles C, Cooke GS, Elliott P, Ward H.",,PloS one,2023,2023-01-26,Y,,,,"

Background

Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.

Methods

People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.

Results

We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.

Conclusion

This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.",,doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render 35448463,https://doi.org/10.3390/metabo12040276,MetaboListem and TABoLiSTM: Two Deep Learning Algorithms for Metabolite Named Entity Recognition.,"Yeung CS, Beck T, Posma JM.",,Metabolites,2022,2022-03-22,Y,Natural Language Processing; Named Entity Recognition; Deep Learning,,,"Reviewing the metabolomics literature is becoming increasingly difficult because of the rapid expansion of relevant journal literature. Text-mining technologies are therefore needed to facilitate more efficient literature reviews. Here we contribute a standardised corpus of full-text publications from metabolomics studies and describe the development of two metabolite named entity recognition (NER) methods. These methods are based on Bidirectional Long Short-Term Memory (BiLSTM) networks and each incorporate different transfer learning techniques (for tokenisation and word embedding). Our first model (MetaboListem) follows prior methodology using GloVe word embeddings. Our second model exploits BERT and BioBERT for embedding and is named TABoLiSTM (Transformer-Affixed BiLSTM). The methods are trained on a novel corpus annotated using rule-based methods, and evaluated on manually annotated metabolomics articles. MetaboListem (F1-score 0.890, precision 0.892, recall 0.888) and TABoLiSTM (BioBERT version: F1-score 0.909, precision 0.926, recall 0.893) have achieved state-of-the-art performance on metabolite NER. A training corpus with full-text sentences from >1000 full-text Open Access metabolomics publications with 105,335 annotated metabolites was created, as well as a manually annotated test corpus (19,138 annotations). This work demonstrates that deep learning algorithms are capable of identifying metabolite names accurately and efficiently in text. The proposed corpus and NER algorithms can be used for metabolomics text-mining tasks such as information retrieval, document classification and literature-based discovery and are available from the omicsNLP GitHub repository.",,doi:https://doi.org/10.3390/metabo12040276; html:https://europepmc.org/articles/PMC9031427; pdf:https://europepmc.org/articles/PMC9031427?pdf=render PMC10464868,https://doi.org/,An overview of synthetic administrative data for research,"Kokosi T, De Stavola B, Mitra R, Frayling L, Doherty A, Dove I, Sonnenberg P, Harron K.",,International journal of population data science,,2023-08-31,Y,Data Linkage; Statistical Disclosure Control; Data Utility; Synthetic Data; Data Confidentiality; Administrative Datasets,,,"Use of administrative data for research and for planning services has increased over recent decades due to the value of the large, rich information available. However, concerns about the release of sensitive or personal data and the associated disclosure risk can lead to lengthy approval processes and restricted data access. This can delay or prevent the production of timely evidence. A promising solution to facilitate more efficient data access is to create synthetic versions of the original datasets which are less likely to hold confidential information and can minimise disclosure risk. Such data may be used as an interim solution, allowing researchers to develop their analysis plans on non-disclosive data, whilst waiting for access to the real data. We aim to provide an overview of the background and uses of synthetic data and describe common methods used to generate synthetic data in the context of UK administrative research. We propose a simplified terminology for categories of synthetic data (univariate, multivariate, and complex modality synthetic data) as well as a more comprehensive description of the terminology used in the existing literature and illustrate challenges and future directions for research.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464868/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464868/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render 35572721,https://doi.org/10.1016/j.eclinm.2022.101419,Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.,"Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,EClinicalMedicine,2022,2022-05-06,Y,School-aged children; Vaccine Effectiveness; Booster Dose; Children Vaccination; Sars-cov-2 Prevalence,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

Department of Health and Social Care, England.",,doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render -37415095,https://doi.org/10.1186/s12889-023-16202-9,Multi-morbidity and its association with common cancer diagnoses: a UK Biobank prospective study.,"Conroy MC, Reeves GK, Allen NE.",,BMC public health,2023,2023-07-06,Y,Cancer Risk; Uk Biobank; Multi-morbidity,,,"

Background

Whilst multi-morbidity is known to be a concern in people with cancer, very little is known about the risk of cancer in multi-morbid patients. This study aims to investigate the risk of being diagnosed with lung, colorectal, breast and prostate cancer associated with multi-morbidity.

Methods

We investigated the association between multi-morbidity and subsequent risk of cancer diagnosis in UK Biobank. Cox models were used to estimate the relative risks of each cancer of interest in multi-morbid participants, using the Cambridge Multimorbidity Score. The extent to which reverse causation, residual confounding and ascertainment bias may have impacted on the findings was robustly investigated.

Results

Of the 436,990 participants included in the study who were cancer-free at baseline, 21.6% (99,965) were multi-morbid (≥ 2 diseases). Over a median follow-up time of 10.9 [IQR 10.0-11.7] years, 9,019 prostate, 7,994 breast, 5,241 colorectal, and 3,591 lung cancers were diagnosed. After exclusion of the first year of follow-up, there was no clear association between multi-morbidity and risk of colorectal, prostate or breast cancer diagnosis. Those with ≥ 4 diseases at recruitment had double the risk of a subsequent lung cancer diagnosis compared to those with no diseases (HR 2.00 [95% CI 1.70-2.35] p for trend < 0.001). These findings were robust to sensitivity analyses aimed at reducing the impact of reverse causation, residual confounding from known cancer risk factors and ascertainment bias.

Conclusions

Individuals with multi-morbidity are at an increased risk of lung cancer diagnosis. While this association did not appear to be due to common sources of bias in observational studies, further research is needed to understand what underlies this association.",,doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?pdf=render 31469943,https://doi.org/10.1002/cnm.3255,Computational instantaneous wave-free ratio (IFR) for patient-specific coronary artery stenoses using 1D network models.,"Carson JM, Roobottom C, Alcock R, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-11-01,Y,Coronary Arteries; Ffr; Ifr; Haemodynamic Modelling,,cardiovascular,"In this work, we estimate the diagnostic threshold of the instantaneous wave-free ratio (iFR) through the use of a one-dimensional haemodynamic framework. To this end, we first compared the computed fractional flow reserve (cFFR) predicted from a 1D computational framework with invasive clinical measurements. The framework shows excellent promise and utilises minimal patient data from a cohort of 52 patients with a total of 66 stenoses. The diagnostic accuracy of the cFFR model was 75.76%, with a sensitivity of 71.43%, a specificity of 77.78%, a positive predictive value of 60%, and a negative predictive value of 85.37%. The validated model was then used to estimate the diagnostic threshold of iFR. The model determined a quadratic relationship between cFFR and the ciFR. The iFR diagnostic threshold was determined to be 0.8910 from a receiver operating characteristic curve that is in the range of 0.89 to 0.9 that is normally reported in clinical studies.",This study aimed to measure how well an algorithm using data from non-invasive tests was able to predict early signs of heart disease.,doi:https://doi.org/10.1002/cnm.3255; html:https://europepmc.org/articles/PMC7003475; pdf:https://europepmc.org/articles/PMC7003475?pdf=render +37415095,https://doi.org/10.1186/s12889-023-16202-9,Multi-morbidity and its association with common cancer diagnoses: a UK Biobank prospective study.,"Conroy MC, Reeves GK, Allen NE.",,BMC public health,2023,2023-07-06,Y,Cancer Risk; Uk Biobank; Multi-morbidity,,,"

Background

Whilst multi-morbidity is known to be a concern in people with cancer, very little is known about the risk of cancer in multi-morbid patients. This study aims to investigate the risk of being diagnosed with lung, colorectal, breast and prostate cancer associated with multi-morbidity.

Methods

We investigated the association between multi-morbidity and subsequent risk of cancer diagnosis in UK Biobank. Cox models were used to estimate the relative risks of each cancer of interest in multi-morbid participants, using the Cambridge Multimorbidity Score. The extent to which reverse causation, residual confounding and ascertainment bias may have impacted on the findings was robustly investigated.

Results

Of the 436,990 participants included in the study who were cancer-free at baseline, 21.6% (99,965) were multi-morbid (≥ 2 diseases). Over a median follow-up time of 10.9 [IQR 10.0-11.7] years, 9,019 prostate, 7,994 breast, 5,241 colorectal, and 3,591 lung cancers were diagnosed. After exclusion of the first year of follow-up, there was no clear association between multi-morbidity and risk of colorectal, prostate or breast cancer diagnosis. Those with ≥ 4 diseases at recruitment had double the risk of a subsequent lung cancer diagnosis compared to those with no diseases (HR 2.00 [95% CI 1.70-2.35] p for trend < 0.001). These findings were robust to sensitivity analyses aimed at reducing the impact of reverse causation, residual confounding from known cancer risk factors and ascertainment bias.

Conclusions

Individuals with multi-morbidity are at an increased risk of lung cancer diagnosis. While this association did not appear to be due to common sources of bias in observational studies, further research is needed to understand what underlies this association.",,doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?pdf=render 34440368,https://doi.org/10.3390/genes12081194,"Genetic Variation in the ASTN2 Locus in Cardiovascular, Metabolic and Psychiatric Traits: Evidence for Pleiotropy Rather Than Shared Biology.","Burt O, Johnston KJA, Graham N, Cullen B, Lyall DM, Lyall LM, Pell JP, Ward J, Smith DJ, Strawbridge RJ.",,Genes,2021,2021-07-31,Y,Blood pressure; BMI; Cardiovascular disease; Metabolic Disease; Psychiatric Illness; Mood Instability; Neuroticism; Central Obesity; Anhedonia; Astn2,,,"

Background

The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The ASTN2 locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of ASTN2 in relation to a wide range of relevant traits.

Methods

Baseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent.

Results

Associations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through ASTN2, however most of the other signals are likely acting through other genes in the locus.

Conclusions

Our systematic analysis demonstrates that ASTN2 has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.",,doi:https://doi.org/10.3390/genes12081194; html:https://europepmc.org/articles/PMC8391428; pdf:https://europepmc.org/articles/PMC8391428?pdf=render 36217535,https://doi.org/10.1038/s43856-022-00185-6,"Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity.","Penney NC, Yeung DKT, Garcia-Perez I, Posma JM, Kopytek A, Garratt B, Ashrafian H, Frost G, Marchesi JR, Purkayastha S, Hoyles L, Darzi A, Holmes E.",,Communications medicine,2022,2022-10-07,Y,Obesity; Type 2 diabetes; Dynamical Systems; Microbiome,,,"

Background

Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.

Methods

To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.

Results

Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.

Conclusion

We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.",,doi:https://doi.org/10.1038/s43856-022-00185-6; html:https://europepmc.org/articles/PMC9546886; pdf:https://europepmc.org/articles/PMC9546886?pdf=render -35909058,https://doi.org/10.1016/s2589-7500(22)00123-6,Remote COVID-19 Assessment in Primary Care (RECAP) risk prediction tool: derivation and real-world validation studies.,"Espinosa-Gonzalez A, Prociuk D, Fiorentino F, Ramtale C, Mi E, Mi E, Glampson B, Neves AL, Okusi C, Husain L, Macartney J, Brown M, Browne B, Warren C, Chowla R, Heaversedge J, Greenhalgh T, de Lusignan S, Mayer E, Delaney BC.",,The Lancet. Digital health,2022,2022-07-28,Y,,,,"

Background

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO2]) and RECAP-oxygen saturation score (RECAP-O2; with SpO2).

Methods

RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people.

Findings

Data were available from 8311 individuals. Observations, such as SpO2, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO2 was available for 1364 (70·0%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0·80 (95% CI 0·76-0·85) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98·1-99·2; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO2 at rest (as a percentage); the area under the curve was 0·84 (0·78-0·90) and on validation the negative predictive value of low risk designation was 99% (95% CI 98·9-99·7; 1176 of 1183).

Interpretation

Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO2 is available, RECAP-O2 is useful to assess the need for treatment escalation.

Funding

Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.",,doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render 36544046,https://doi.org/10.1038/s41746-022-00730-6,A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.,"Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.",,NPJ digital medicine,2022,2022-12-21,Y,,,,"Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n = 94; £ = 41.97 m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.",,doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render +35909058,https://doi.org/10.1016/s2589-7500(22)00123-6,Remote COVID-19 Assessment in Primary Care (RECAP) risk prediction tool: derivation and real-world validation studies.,"Espinosa-Gonzalez A, Prociuk D, Fiorentino F, Ramtale C, Mi E, Mi E, Glampson B, Neves AL, Okusi C, Husain L, Macartney J, Brown M, Browne B, Warren C, Chowla R, Heaversedge J, Greenhalgh T, de Lusignan S, Mayer E, Delaney BC.",,The Lancet. Digital health,2022,2022-07-28,Y,,,,"

Background

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO2]) and RECAP-oxygen saturation score (RECAP-O2; with SpO2).

Methods

RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people.

Findings

Data were available from 8311 individuals. Observations, such as SpO2, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO2 was available for 1364 (70·0%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0·80 (95% CI 0·76-0·85) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98·1-99·2; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO2 at rest (as a percentage); the area under the curve was 0·84 (0·78-0·90) and on validation the negative predictive value of low risk designation was 99% (95% CI 98·9-99·7; 1176 of 1183).

Interpretation

Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO2 is available, RECAP-O2 is useful to assess the need for treatment escalation.

Funding

Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.",,doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render 32851419,https://doi.org/10.1007/s00394-020-02372-4,Vitamin D and COVID-19 infection and mortality in UK Biobank.,"Hastie CE, Pell JP, Sattar N.",,European journal of nutrition,2021,2020-08-26,Y,Vitamin D; Mortality; Covid-19,,,"

Purpose

Low blood 25-hydroxyvitamin D (25(OH)D) concentration has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether baseline serum 25(OH)D concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants.

Methods

UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including serum 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and Poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection.

Results

Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. 25(OH)D concentration was associated with severe COVID-19 infection and mortality univariably (mortality per 10 nmol/L 25(OH)D HR  0.92; 95% CI 0.86-0.98; p = 0.016), but not after adjustment for confounders (mortality per 10 nmol/L 25(OH)D HR 0.98; 95% CI = 0.91-1.06; p = 0.696). Vitamin D insufficiency or deficiency was also not independently associated with either COVID-19 infection or linked mortality.

Conclusions

Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality. Randomised trials are needed to prove a beneficial role for vitamin D in the prevention of severe COVID-19 reactions or death.",,doi:https://doi.org/10.1007/s00394-020-02372-4; html:https://europepmc.org/articles/PMC7449523; pdf:https://europepmc.org/articles/PMC7449523?pdf=render 32935051,https://doi.org/10.23889/ijpds.v5i1.1128,A national initiative in data science for health: an evaluation of the UK Farr Institute.,"Hemingway H, Lyons R, Li Q, Buchan I, Ainsworth J, Pell J, Morris A.",,International journal of population data science,2020,2020-04-08,Y,,,,"

Objective

To evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK.

Design and outcome measures

We evaluated evidence of six domains characterising a new field of science:defining central scientific challenges,demonstrating how the central challenges might be solved,creating novel interactions among groups of scientists,training new types of experts,re-organising universities,demonstrating impacts in society.We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools.

Setting

Four UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018.

Results

1. The Farr Institute helped define a central scientific challenge publishing a research corpus, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. 2. The Farr Institute offered some demonstrations of how these scientific challenges might be solved: it established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 research users, published on 102 unique EHR and administrative data sources, although there was no clear evidence of an increase in novel, sustained record linkages. The Farr Institute established open platforms for the EHR phenotyping algorithms and validations (>70 diseases, CALIBER). Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. 3.The Farr Institute created novel interactions among researchers: the co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4. Training expanded substantially with 3 new masters courses, training >400 people at masters, short-course and leadership level and 48 PhD students. 5. Universities reorganised with 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes. 6. Emerging evidence of impacts included: > 3200 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens.

Conclusion

The Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research (HDR) UK but key challenges remain including, how to network such activities internationally.",,doi:https://doi.org/10.23889/ijpds.v5i1.1128; html:https://europepmc.org/articles/PMC7480324; pdf:https://europepmc.org/articles/PMC7480324?pdf=render 35336739,https://doi.org/10.3390/biology11030365,Machine Learning-Based Identification of Colon Cancer Candidate Diagnostics Genes. ,"Koppad S, Basava A, Nash K, Gkoutos GV, Acharjee A.",,Biology,2022,2022-02-25,Y,,,,"Colorectal cancer (CRC) is the third leading cause of cancer-related death and the fourth most commonly diagnosed cancer worldwide. Due to a lack of diagnostic biomarkers and understanding of the underlying molecular mechanisms, CRC's mortality rate continues to grow. CRC occurrence and progression are dynamic processes. The expression levels of specific molecules vary at various stages of CRC, rendering its early detection and diagnosis challenging and the need for identifying accurate and meaningful CRC biomarkers more pressing. The advances in high-throughput sequencing technologies have been used to explore novel gene expression, targeted treatments, and colon cancer pathogenesis. Such approaches are routinely being applied and result in large datasets whose analysis is increasingly becoming dependent on machine learning (ML) algorithms that have been demonstrated to be computationally efficient platforms for the identification of variables across such high-dimensional datasets. We developed a novel ML-based experimental design to study CRC gene associations. Six different machine learning methods were employed as classifiers to identify genes that can be used as diagnostics for CRC using gene expression and clinical datasets. The accuracy, sensitivity, specificity, F1 score, and area under receiver operating characteristic (AUROC) curve were derived to explore the differentially expressed genes (DEGs) for CRC diagnosis. Gene ontology enrichment analyses of these DEGs were performed and predicted gene signatures were linked with miRNAs. We evaluated six machine learning classification methods (Adaboost, ExtraTrees, logistic regression, naïve Bayes classifier, random forest, and XGBoost) across different combinations of training and test datasets over GEO datasets. The accuracy and the AUROC of each combination of training and test data with different algorithms were used as comparison metrics. Random forest (RF) models consistently performed better than other models. In total, 34 genes were identified and used for pathway and gene set enrichment analysis. Further mapping of the 34 genes with miRNA identified interesting miRNA hubs genes. We identified 34 genes with high accuracy that can be used as a diagnostics panel for CRC.",,doi:https://doi.org/10.3390/biology11030365; html:https://europepmc.org/articles/PMC8944988; pdf:https://europepmc.org/articles/PMC8944988?pdf=render 34007894,https://doi.org/10.23889/ijpds.v6i1.1373,Visualisation and optimisation of alcohol-related hospital admissions ICD-10 codes in Welsh e-cohort data.,"Trefan L, Akbari A, Morgan JS, Farewell DM, Fone D, Lyons RA, Jones Hywel M, Moore SC.",,International journal of population data science,2021,2021-03-24,Y,Alcohol; Hospital Admission; Optimisation; Icd-10 Codes; E-Cohort Data,,,"

Introduction

The excessive consumption of alcohol is detrimental to long term health and increases the likelihood of hospital admission. However, definitions of alcohol-related hospital admission vary, giving rise to uncertainty in the effect of alcohol on alcohol-related health care utilization.

Objectives

To compare diagnostic codes on hospital admission and discharge and to determine the ideal combination of codes necessary for an accurate determination of alcohol-related hospital admission.

Methods

Routine population-linked e-cohort data were extracted from the Secure Anonymised Information Linkage (SAIL) Databank containing all alcohol-related hospital admissions (n,= 92,553) from 2006 to 2011 in Wales, United Kingdom. The distributions of the diagnostic codes recorded at admission and discharge were compared. By calculating a misclassification rate (sensitivity-like measure) the appropriate number of coding fields to examine for alcohol-codes was established.

Results

There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.

Conclusion

With the data at present and alcohol-related codes used, codes recorded at admission and discharge can be used equivalently to identify alcohol-related admissions. The appropriate number of coding fields to examine was established: fewer than ten is likely to lead to under-reporting of alcohol-related admissions. The methods developed here can be applied to other medical conditions that can be described using a certain set of diagnostic codes, each of which can be a known sole cause of the condition and recorded in multiple positions in e-cohort data.",,doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?pdf=render 37340474,https://doi.org/10.1186/s12916-023-02877-9,Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.,"Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",,BMC medicine,2023,2023-06-21,Y,Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2,,,"

Background

Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.

Methods

Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.

Results

AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.

Conclusions

This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",,doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render 35189888,https://doi.org/10.1186/s12916-022-02286-4,Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK).,"Talaei M, Faustini S, Holt H, Jolliffe DA, Vivaldi G, Greenig M, Perdek N, Maltby S, Bigogno CM, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Richter AG, Shaheen SO, Martineau AR.",,BMC medicine,2022,2022-02-22,Y,Obesity; Diet; Serology; Alcohol; Exercise; Micronutrients; Lifestyle; Ethnicity; Occupation; Sars-cov-2,,,"

Background

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

Methods

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

Results

Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06-1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11-1.39), South Asian vs. White ethnicity (1.65, 1.10-2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with  lower risk (0.80, 0.70-0.93, for ≥ 10 vs. 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02-1.19), South Asian vs. White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02-1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.

Conclusions

Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.",,doi:https://doi.org/10.1186/s12916-022-02286-4; html:https://europepmc.org/articles/PMC8860623; pdf:https://europepmc.org/articles/PMC8860623?pdf=render -35492818,https://doi.org/10.1016/j.jaccao.2022.01.102,Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?: An English Retrospective Cohort Study.,"Strongman H, Gadd S, Matthews AA, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.",,JACC. CardioOncology,2022,2022-03-15,Y,"Electronic Health Records; Cancer Survivors; Beyond Cancer; Cprd Gold, Clinical Practice Research Datalink Primary Care Data In England",,,"

Background

Cancer survivors have a higher risk for developing cardiovascular diseases than the general population.

Objectives

The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death.

Methods

This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults ≥40 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation.

Results

Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types ≥80 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the ≥80-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer.

Conclusions

In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.",,doi:https://doi.org/10.1016/j.jaccao.2022.01.102; html:https://europepmc.org/articles/PMC9040113; pdf:https://europepmc.org/articles/PMC9040113?pdf=render 33745917,https://doi.org/10.1016/j.jinf.2021.03.011,"The dynamics of procalcitonin in COVID-19 patients admitted to Intensive care unit - a multi-centre cohort study in the South West of England, UK.","Williams P, McWilliams C, Soomro K, Harding I, Gurney S, Thomas M, Albur M, Martin Williams O.",,The Journal of infection,2021,2021-03-18,Y,,,,,,doi:https://doi.org/10.1016/j.jinf.2021.03.011; html:https://europepmc.org/articles/PMC7970419; pdf:https://europepmc.org/articles/PMC7970419?pdf=render +35492818,https://doi.org/10.1016/j.jaccao.2022.01.102,Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?: An English Retrospective Cohort Study.,"Strongman H, Gadd S, Matthews AA, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.",,JACC. CardioOncology,2022,2022-03-15,Y,"Electronic Health Records; Cancer Survivors; Beyond Cancer; Cprd Gold, Clinical Practice Research Datalink Primary Care Data In England",,,"

Background

Cancer survivors have a higher risk for developing cardiovascular diseases than the general population.

Objectives

The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death.

Methods

This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults ≥40 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation.

Results

Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types ≥80 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the ≥80-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer.

Conclusions

In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.",,doi:https://doi.org/10.1016/j.jaccao.2022.01.102; html:https://europepmc.org/articles/PMC9040113; pdf:https://europepmc.org/articles/PMC9040113?pdf=render 35595824,https://doi.org/10.1038/s41598-022-12517-6,Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK.,"Waites W, Pearson CAB, Gaskell KM, House T, Pellis L, Johnson M, Gould V, Hunt A, Stone NRH, Kasstan B, Chantler T, Lal S, Roberts CH, Goldblatt D, CMMID COVID-19 Working Group, Marks M, Eggo RM.",,Scientific reports,2022,2022-05-20,Y,,,,"Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.",,doi:https://doi.org/10.1038/s41598-022-12517-6; html:https://europepmc.org/articles/PMC9121858; pdf:https://europepmc.org/articles/PMC9121858?pdf=render 31799783,https://doi.org/10.1002/cnm.3267,Personalising cardiovascular network models in pregnancy: A two-tiered parameter estimation approach.,"Carson J, Warrander L, Johnstone E, van Loon R.",,International journal for numerical methods in biomedical engineering,2021,2020-01-13,Y,Pregnancy; Parameter estimation; Pre-eclampsia; Personalised Haemodynamic Model; Uterine Artery Waveform,,,"Uterine artery Doppler waveforms are often studied to determine whether a patient is at risk of developing pathologies such as pre-eclampsia. Many uterine waveform indices have been developed, which attempt to relate characteristics of the waveform with the physiological adaptation of the maternal cardiovascular system, and are often suggested to be an indicator of increased placenta resistance and arterial stiffness. Doppler waveforms of four patients, two of whom developed pre-eclampsia, are compared with a comprehensive closed-loop model of pregnancy. The closed-loop model has been previously validated but has been extended to include an improved parameter estimation technique that utilises systolic and diastolic blood pressure, cardiac output, heart rate, and pulse wave velocity measurements to adapt model resistances, compliances, blood volume, and the mean vessel areas in the main systemic arteries. The shape of the model-predicted uterine artery velocity waveforms showed good agreement with the characteristics observed in the patient Doppler waveforms. The personalised models obtained now allow a prediction of the uterine pressure waveforms in addition to the uterine velocity. This allows for a more detailed mechanistic analysis of the waveforms, eg, wave intensity analysis, to study existing clinical indices. The findings indicate that to accurately estimate arterial stiffness, both pulse pressure and pulse wave velocities are required. In addition, the results predict that patients who developed pre-eclampsia later in pregnancy have larger vessel areas in the main systemic arteries compared with the two patients who had normal pregnancy outcomes.",,doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?pdf=render 37536152,https://doi.org/10.1016/j.seizure.2023.07.016,Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.,"Josephson CB, Gonzalez-Izquierdo A, Engbers JDT, Denaxas S, Delgado-Garcia G, Sajobi TT, Wang M, Keezer MR, Wiebe S.",,Seizure,2023,2023-07-29,N,Epilepsy; Elderly; Cohort study; Electronic Health Records; Unsupervised Machine Learning; Late-onset Epilepsy,,,"

Background and objectives

Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.

Methods

We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.

Results

From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.

Significance

Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.",,doi:https://doi.org/10.1016/j.seizure.2023.07.016 @@ -283,35 +284,35 @@ PMC10464868,https://doi.org/,An overview of synthetic administrative data for re 36333839,https://doi.org/10.1002/gps.5834,The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.,"Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.",,International journal of geriatric psychiatry,2022,2022-10-24,Y,Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity,,,"

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.",,doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render 31088492,https://doi.org/10.1186/s12967-019-1912-5,-Omics biomarker identification pipeline for translational medicine.,"Bravo-Merodio L, Williams JA, Gkoutos GV, Acharjee A.",,Journal of translational medicine,2019,2019-05-14,Y,Biomarker; Feature Selection; Regularization; -omics; Translational Medicine,,,"

Background

Translational medicine (TM) is an emerging domain that aims to facilitate medical or biological advances efficiently from the scientist to the clinician. Central to the TM vision is to narrow the gap between basic science and applied science in terms of time, cost and early diagnosis of the disease state. Biomarker identification is one of the main challenges within TM. The identification of disease biomarkers from -omics data will not only help the stratification of diverse patient cohorts but will also provide early diagnostic information which could improve patient management and potentially prevent adverse outcomes. However, biomarker identification needs to be robust and reproducible. Hence a robust unbiased computational framework that can help clinicians identify those biomarkers is necessary.

Methods

We developed a pipeline (workflow) that includes two different supervised classification techniques based on regularization methods to identify biomarkers from -omics or other high dimension clinical datasets. The pipeline includes several important steps such as quality control and stability of selected biomarkers. The process takes input files (outcome and independent variables or -omics data) and pre-processes (normalization, missing values) them. After a random division of samples into training and test sets, Least Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods are applied to identify the most important features representing potential biomarker candidates. The penalization parameters are optimised using 10-fold cross validation and the process undergoes 100 iterations and a combinatorial analysis to select the best performing multivariate model. An empirical unbiased assessment of their quality as biomarkers for clinical use is performed through a Receiver Operating Characteristic curve and its Area Under the Curve analysis on both permuted and real data for 1000 different randomized training and test sets. We validated this pipeline against previously published biomarkers.

Results

We applied this pipeline to three different datasets with previously published biomarkers: lipidomics data by Acharjee et al. (Metabolomics 13:25, 2017) and transcriptomics data by Rajamani and Bhasin (Genome Med 8:38, 2016) and Mills et al. (Blood 114:1063-1072, 2009). Our results demonstrate that our method was able to identify both previously published biomarkers as well as new variables that add value to the published results.

Conclusions

We developed a robust pipeline to identify clinically relevant biomarkers that can be applied to different -omics datasets. Such identification reveals potentially novel drug targets and can be used as a part of a machine-learning based patient stratification framework in the translational medicine settings.",,doi:https://doi.org/10.1186/s12967-019-1912-5; html:https://europepmc.org/articles/PMC6518609; pdf:https://europepmc.org/articles/PMC6518609?pdf=render 35289755,https://doi.org/10.2196/31021,Concept Libraries for Repeatable and Reusable Research: Qualitative Study Exploring the Needs of Users.,"Almowil Z, Zhou SM, Brophy S, Croxall J.",,JMIR human factors,2022,2022-03-15,Y,Electronic Health Records; Record Linkage; Reproducible Research; Clinical Codes; Concept Libraries,,,"

Background

Big data research in the field of health sciences is hindered by a lack of agreement on how to identify and define different conditions and their medications. This means that researchers and health professionals often have different phenotype definitions for the same condition. This lack of agreement makes it difficult to compare different study findings and hinders the ability to conduct repeatable and reusable research.

Objective

This study aims to examine the requirements of various users, such as researchers, clinicians, machine learning experts, and managers, in the development of a data portal for phenotypes (a concept library).

Methods

This was a qualitative study using interviews and focus group discussion. One-to-one interviews were conducted with researchers, clinicians, machine learning experts, and senior research managers in health data science (N=6) to explore their specific needs in the development of a concept library. In addition, a focus group discussion with researchers (N=14) working with the Secured Anonymized Information Linkage databank, a national eHealth data linkage infrastructure, was held to perform a SWOT (strengths, weaknesses, opportunities, and threats) analysis for the phenotyping system and the proposed concept library. The interviews and focus group discussion were transcribed verbatim, and 2 thematic analyses were performed.

Results

Most of the participants thought that the prototype concept library would be a very helpful resource for conducting repeatable research, but they specified that many requirements are needed before its development. Although all the participants stated that they were aware of some existing concept libraries, most of them expressed negative perceptions about them. The participants mentioned several facilitators that would stimulate them to share their work and reuse the work of others, and they pointed out several barriers that could inhibit them from sharing their work and reusing the work of others. The participants suggested some developments that they would like to see to improve reproducible research output using routine data.

Conclusions

The study indicated that most interviewees valued a concept library for phenotypes. However, only half of the participants felt that they would contribute by providing definitions for the concept library, and they reported many barriers regarding sharing their work on a publicly accessible platform. Analysis of interviews and the focus group discussion revealed that different stakeholders have different requirements, facilitators, barriers, and concerns about a prototype concept library.",,doi:https://doi.org/10.2196/31021; html:https://europepmc.org/articles/PMC8965669 -37434746,https://doi.org/10.1016/j.eclinm.2023.102077,"Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.","Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.",,EClinicalMedicine,2023,2023-06-29,Y,Pandemic; Healthcare Utilisation; Ethnic Differences,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).",,doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render 33517931,https://doi.org/10.1192/j.eurpsy.2021.6,"The association between C-reactive protein, mood disorder, and cognitive function in UK Biobank.","Milton DC, Ward J, Ward E, Lyall DM, Strawbridge RJ, Smith DJ, Cullen B.",,European psychiatry : the journal of the Association of European Psychiatrists,2021,2021-02-01,Y,Inflammation; Cognitive function; C-reactive Protein; Mood Disorder,,,"

Background

Systemic inflammation has been linked with mood disorder and cognitive impairment. The extent of this relationship remains uncertain, with the effects of serum inflammatory biomarkers compared to genetic predisposition toward inflammation yet to be clearly established.

Methods

We investigated the magnitude of associations between C-reactive protein (CRP) measures, lifetime history of bipolar disorder or major depression, and cognitive function (reaction time and visuospatial memory) in 84,268 UK Biobank participants. CRP was measured in serum and a polygenic risk score for CRP was calculated, based on a published genome-wide association study. Multiple regression models adjusted for sociodemographic and clinical confounders.

Results

Increased serum CRP was significantly associated with mood disorder history (Kruskal-Wallis H = 196.06, p < 0.001, η2 = 0.002) but increased polygenic risk for CRP was not (F = 0.668, p = 0.648, η2 < 0.001). Compared to the lowest quintile, the highest serum CRP quintile was significantly associated with both negative and positive differences in cognitive performance (fully adjusted models: reaction time B = -0.030, 95% CI = -0.052, -0.008; visuospatial memory B = 0.066, 95% CI = 0.042, 0.089). More severe mood disorder categories were significantly associated with worse cognitive performance and this was not moderated by serum or genetic CRP level.

Conclusions

In this large cohort study, we found that measured inflammation was associated with mood disorder history, but genetic predisposition to inflammation was not. The association between mood disorder and worse cognitive performance was very small and did not vary by CRP level. The inconsistent relationship between CRP measures and cognitive performance warrants further study.",,doi:https://doi.org/10.1192/j.eurpsy.2021.6; html:https://europepmc.org/articles/PMC8057439; pdf:https://europepmc.org/articles/PMC8057439?pdf=render 35050151,https://doi.org/10.3390/metabo12010029,Integration of Metabolomic and Clinical Data Improves the Prediction of Intensive Care Unit Length of Stay Following Major Traumatic Injury. ,"Acharjee A, Hazeldine J, Bazarova A, Deenadayalu L, Zhang J, Bentley C, Russ D, Lord JM, Gkoutos GV, Young SP, Foster MA.",,Metabolites,2021,2021-12-31,Y,,,,"Recent advances in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients now reach the hospital alive and survive life-saving operations. Indeed, between 2008 and 2017, the odds of surviving a major traumatic injury in the UK increased by nineteen percent. However, the improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥10 days. Improved understanding of the factors influencing patient outcomes is now urgently needed. We investigated the serum metabolomic profile of fifty-five major trauma patients across three post-injury phases: acute (days 0-4), intermediate (days 5-14) and late (days 15-112). Using ICU length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0-4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (<10 days) ICU LOS. In addition, we investigated whether combining metabolomic profiles with clinical scoring systems would generate a variable that would identify patients with an extended ICU LOS with a greater degree of accuracy than models built on either variable alone. The number of metabolites unique to and shared across each time segment varied across acute, intermediate and late segments. A one-way ANOVA revealed the most variation in metabolite levels across the different time-points was for the metabolites lactate, glucose, anserine and 3-hydroxybutyrate. A total of eleven features were selected to differentiate between <10 days ICU LOS vs. >10 days ICU LOS. New Injury Severity Score (NISS), testosterone, and the metabolites cadaverine, urea, isoleucine, acetoacetate, dimethyl sulfone, syringate, creatinine, xylitol, and acetone form the integrated biomarker set. Using metabolic enrichment analysis, we found valine, leucine and isoleucine biosynthesis, glutathione metabolism, and glycine, serine and threonine metabolism were the top three pathways differentiating ICU LOS with a p < 0.05. A combined model of NISS and testosterone and all nine selected metabolites achieved an AUROC of 0.824. Differences exist in the serum metabolome of major trauma patients who subsequently experience a short or prolonged ICU LOS in the acute post-injury setting. Combining metabolomic data with anatomical scoring systems allowed us to discriminate between these two groups with a greater degree of accuracy than that of either variable alone.",,doi:https://doi.org/10.3390/metabo12010029; html:https://europepmc.org/articles/PMC8780653; pdf:https://europepmc.org/articles/PMC8780653?pdf=render 34340970,https://doi.org/10.3399/bjgp.2021.0301,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.,"Walker AJ, MacKenna B, Inglesby P, Tomlinson L, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19; Long Covid,,,"

Background

Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.

Aim

To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.

Design and setting

Population-based cohort study in English primary care.

Method

Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.

Results

Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).

Conclusion

Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.",,doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render -37337233,https://doi.org/10.1186/s12916-023-02921-8,Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.,"Kimenai DM, Anand A, de Bakker M, Shipley M, Fujisawa T, Lyngbakken MN, Hveem K, Omland T, Valencia-Hernández CA, Lindbohm JV, Kivimaki M, Singh-Manoux A, Strachan FE, Shah ASV, Kardys I, Boersma E, Brunner EJ, Mills NL.",,BMC medicine,2023,2023-06-19,Y,cardiac troponin; risk factors; Outcome; General Population,,,"

Background

High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.

Methods

In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements.

Results

In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75).

Conclusions

Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.",,doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?pdf=render 32565483,https://doi.org/10.1136/bmjopen-2020-039097,Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II): protocol for an observational study using linked Scottish national data.,"Simpson CR, Robertson C, Vasileiou E, McMenamin J, Gunson R, Ritchie LD, Woolhouse M, Morrice L, Kelly D, Stagg HR, Marques D, Murray J, Sheikh A.",,BMJ open,2020,2020-06-21,Y,epidemiology; Public Health; Respiratory Medicine (See Thoracic Medicine),,,"

Introduction

Following the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 and the ensuing COVID-19 pandemic, population-level surveillance and rapid assessment of the effectiveness of existing or new therapeutic or preventive interventions are required to ensure that interventions are targeted to those at highest risk of serious illness or death from COVID-19. We aim to repurpose and expand an existing pandemic reporting platform to determine the attack rate of SARS-CoV-2, the uptake and effectiveness of any new pandemic vaccine (once available) and any protective effect conferred by existing or new antimicrobial drugs and other therapies.

Methods and analysis

A prospective observational cohort will be used to monitor daily/weekly the progress of the COVID-19 epidemic and to evaluate the effectiveness of therapeutic interventions in approximately 5.4 million individuals registered in general practices across Scotland. A national linked dataset of patient-level primary care data, out-of-hours, hospitalisation, mortality and laboratory data will be assembled. The primary outcomes will measure association between: (A) laboratory confirmed SARS-CoV-2 infection, morbidity and mortality, and demographic, socioeconomic and clinical population characteristics; and (B) healthcare burden of COVID-19 and demographic, socioeconomic and clinical population characteristics. The secondary outcomes will estimate: (A) the uptake (for vaccines only); (B) effectiveness; and (C) safety of new or existing therapies, vaccines and antimicrobials against SARS-CoV-2 infection. The association between population characteristics and primary outcomes will be assessed via multivariate logistic regression models. The effectiveness of therapies, vaccines and antimicrobials will be assessed from time-dependent Cox models or Poisson regression models. Self-controlled study designs will be explored to estimate the risk of therapeutic and prophylactic-related adverse events.

Ethics and dissemination

We obtained approval from the National Research Ethics Service Committee, Southeast Scotland 02. The study findings will be presented at international conferences and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2020-039097; html:https://europepmc.org/articles/PMC7311023; pdf:https://europepmc.org/articles/PMC7311023?pdf=render +37337233,https://doi.org/10.1186/s12916-023-02921-8,Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.,"Kimenai DM, Anand A, de Bakker M, Shipley M, Fujisawa T, Lyngbakken MN, Hveem K, Omland T, Valencia-Hernández CA, Lindbohm JV, Kivimaki M, Singh-Manoux A, Strachan FE, Shah ASV, Kardys I, Boersma E, Brunner EJ, Mills NL.",,BMC medicine,2023,2023-06-19,Y,cardiac troponin; risk factors; Outcome; General Population,,,"

Background

High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.

Methods

In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements.

Results

In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75).

Conclusions

Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.",,doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?pdf=render 36987388,https://doi.org/10.1177/08862605231163885,Characterizing the Differences in Descriptions of Violence on Reddit During the COVID-19 Pandemic.,"Li L, Neubauer L, Stewart R, Roberts A.",,Journal of interpersonal violence,2023,2023-03-28,Y,Increase rate; Data Classification; Reddit; Violence Types,,,"Concerns have been raised over the experiences of violence such as domestic violence (DV) and intimate partner violence (IPV) during the COVID-19 pandemic. Social media such as Reddit represent an alternative outlet for reporting experiences of violence where healthcare access has been limited. This study analyzed seven violence-related subreddits to investigate the trends of different violence patterns from January 2018 to February 2022 to enhance the health-service providers' existing service or provide some new perspective for existing violence research. Specifically, we collected violence-related texts from Reddit using keyword searching and identified six major types with supervised machine learning classifiers: DV, IPV, physical violence, sexual violence, emotional violence, and nonspecific violence or others. The increase rate (IR) of each violence type was calculated and temporally compared in five phases of the pandemic. The phases include one pre-pandemic phase (Phase 0, the date before February 26, 2020) and four pandemic phases (Phases 1-4) with separation dates of June 17, 2020, September 7, 2020, and June 4, 2021. We found that the number of IPV-related posts increased most in the earliest phase; however, that for COVID-citing IPV was highest in the mid-pandemic phase. IRs for DV, IPV, and emotional violence also showed increases across all pandemic phases, with IRs of 26.9%, 58.8%, and 28.8%, respectively, from the pre-pandemic to the first pandemic phase. In the other three pandemic phases, all the IRs for these three types of violence were positive, though lower than the IRs in the first pandemic phase. The findings highlight the importance of identifying and providing help to those who suffer from such violent experiences and support the role of social media site monitoring as a means of informative surveillance for help-providing authorities and violence research groups.",,doi:https://doi.org/10.1177/08862605231163885; html:https://europepmc.org/articles/PMC10064198; pdf:https://europepmc.org/articles/PMC10064198?pdf=render 37596262,https://doi.org/10.1038/s41467-023-40679-y,A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.,"Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ.",,Nature communications,2023,2023-08-18,Y,,,,"Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.",,doi:https://doi.org/10.1038/s41467-023-40679-y; html:https://europepmc.org/articles/PMC10439125; pdf:https://europepmc.org/articles/PMC10439125?pdf=render 35413949,https://doi.org/10.1038/s41467-022-29521-z,"Persistent COVID-19 symptoms in a community study of 606,434 people in England.","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,Nature communications,2022,2022-04-12,Y,,,,"Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.",,doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render +37434746,https://doi.org/10.1016/j.eclinm.2023.102077,"Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.","Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.",,EClinicalMedicine,2023,2023-06-29,Y,Pandemic; Healthcare Utilisation; Ethnic Differences,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).",,doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render 32405103,https://doi.org/10.1016/s0140-6736(20)30854-0,Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study.,"Banerjee A, Pasea L, Harris S, Gonzalez-Izquierdo A, Torralbo A, Shallcross L, Noursadeghi M, Pillay D, Sebire N, Holmes C, Pagel C, Wong WK, Langenberg C, Williams B, Denaxas S, Hemingway H.",,"Lancet (London, England)",2020,2020-05-12,Y,,,,"

Background

The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease.

Methods

In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation.

Findings

We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41-4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0.

Interpretation

We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality.

Funding

National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.","This paper aims to estimate the excess number of deaths over 1 year associated with covid-19, based on age and underlying conditions. They found that age, sex and underlying conditions do influence background risk, and support the need for sustained stringent suppression measures. They have also developed an online risk calculator prototype which is openly available for anyone to use.",doi:https://doi.org/10.1016/S0140-6736(20)30854-0; html:https://europepmc.org/articles/PMC7217641 -35192611,https://doi.org/10.1371/journal.pmed.1003916,Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.,"McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.",,PLoS medicine,2022,2022-02-22,Y,,,,"

Background

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

Methods and findings

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

Conclusions

In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render 34598993,https://doi.org/10.1136/bmjopen-2021-054410,"Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.","Greenbury SF, Longford N, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,BMJ open,2021,2021-10-01,Y,Public Health; Neonatology; Neonatal Intensive & Critical Care,,,"

Objectives

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

Design

Observational cohort study using the UK National Neonatal Research Database.

Setting

England and Wales.

Participants

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

Main outcome measures

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

Methods

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

Results

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

Conclusions

Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.",,doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render +35192611,https://doi.org/10.1371/journal.pmed.1003916,Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.,"McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.",,PLoS medicine,2022,2022-02-22,Y,,,,"

Background

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

Methods and findings

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

Conclusions

In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render 33780469,https://doi.org/10.1371/journal.pone.0248195,Deriving household composition using population-scale electronic health record data-A reproducible methodology. ,"Johnson RD, Griffiths LJ, Hollinghurst JP, Akbari A, Lee A, Thompson DA, Lyons RA, Fry R.",,PloS one,2021,2021-03-29,Y,,,,"Physical housing and household composition have an important role in the lives of individuals and drive health and social outcomes, and inequalities. Most methods to understand housing composition are based on survey or census data, and there is currently no reproducible methodology for creating population-level household composition measures using linked administrative data. Using existing, and more recent enhancements to the address-data linkage methods in the SAIL Databank using Residential Anonymised Linking Fields we linked individuals to properties using the anonymised Welsh Demographic Service data in the SAIL Databank. We defined households, household size, and household composition measures based on adult to child relationships, and age differences between residents to create relative age measures. Two relative age-based algorithms were developed and returned similar results when applied to population and household-level data, describing household composition for 3.1 million individuals within 1.2 million households in Wales. Developed methods describe binary, and count level generational household composition measures. Improved residential anonymised linkage field methods in SAIL have led to improved property-level data linkage, allowing the design and application of household composition measures that assign individuals to shared residences and allow the description of household composition across Wales. The reproducible methods create longitudinal, household-level composition measures at a population-level using linked administrative data. Such measures are important to help understand more detail about an individual's home and area environment and how that may affect the health and wellbeing of the individual, other residents, and potentially into the wider community.",,doi:https://doi.org/10.1371/journal.pone.0248195; html:https://europepmc.org/articles/PMC8007012; pdf:https://europepmc.org/articles/PMC8007012?pdf=render 33087383,https://doi.org/10.1136/bmjopen-2020-043010,Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions. ,"Lyons J, Akbari A, Torabi F, Davies GI, North L, Griffiths R, Bailey R, Hollinghurst J, Fry R, Turner SL, Thompson D, Rafferty J, Mizen A, Orton C, Thompson S, Au-Yeung L, Cross L, Gravenor MB, Brophy S, Lucini B, John A, Szakmany T, Davies J, Davies C, Thomas DR, Williams C, Emmerson C, Cottrell S, Connor TR, Taylor C, Pugh RJ, Diggle P, John G, Scourfield S, Hunt J, Cunningham AM, Helliwell K, Lyons R.",,BMJ open,2020,2020-10-21,Y,,,,"The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions. Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection. The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?pdf=render 36332942,https://doi.org/10.1136/openhrt-2022-002142,Development of algorithms for determining heart failure with reduced and preserved ejection fraction using nationwide electronic healthcare records in the UK.,"Sundaram V, Zakeri R, Witte KK, Quint JK.",,Open heart,2022,2022-11-01,Y,epidemiology; Heart Failure; Electronic Health Records,,,"

Background

Determining heart failure (HF) phenotypes in routine electronic health records (EHR) is challenging. We aimed to develop and validate EHR algorithms for identification of specific HF phenotypes, using Read codes in combination with selected patient characteristics.

Methods

We used The Healthcare Improvement Network (THIN). The study population included a random sample of individuals with HF diagnostic codes (HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF) and non-specific HF) selected from all participants registered in the THIN database between 1 January 2015 and 30 September 2017. Confirmed diagnoses were determined in a randomly selected subgroup of 500 patients via GP questionnaires including a review of all available cardiovascular investigations. Confirmed diagnoses of HFrEF and HFpEF were based on four criteria. Based on these data, we calculated a positive predictive value (PPV) of predefined algorithms which consisted of a combination of Read codes and additional information such as echocardiogram results and HF medication records.

Results

The final cohort from which we drew the 500 patient random sample consisted of 10 275 patients. Response rate to the questionnaire was 77.2%. A small proportion (18%) of the overall HF patient population were coded with specific HF phenotype Read codes. For HFrEF, algorithms achieving over 80% PPV included definite, possible or non-specific HF HFrEF codes when combined with at least two of the drugs used to treat HFrEF. Only in non-specific HF coding did the use of three drugs (rather than two) contribute to an improvement of the PPV for HFrEF. HFpEF was only accurately defined with specific codes. In the absence of specific coding for HFpEF, the PPV was consistently below 50%.

Conclusions

Prescription for HF medication can reliably be used to find HFrEF patients in the UK, even in the absence of a specific Read code for HFrEF. Algorithms using non-specific coding could not reliably find HFpEF patients.",,doi:https://doi.org/10.1136/openhrt-2022-002142; html:https://europepmc.org/articles/PMC9639145; pdf:https://europepmc.org/articles/PMC9639145?pdf=render 32635913,https://doi.org/10.1186/s12911-020-01169-z,Application of standardised effect sizes to hospital discharge outcomes for people with diabetes.,"Robbins T, Lim Choi Keung SN, Sankar S, Randeva H, Arvanitis TN.",,BMC medical informatics and decision making,2020,2020-07-07,Y,Mortality; Diabetes; Readmission; Effect Size,,,"

Background

Patients with diabetes are at an increased risk of readmission and mortality when discharged from hospital. Existing research identifies statistically significant risk factors that are thought to underpin these outcomes. Increasingly, these risk factors are being used to create risk prediction models, and target risk modifying interventions. These risk factors are typically reported in the literature accompanied by unstandardized effect sizes, which makes comparisons difficult. We demonstrate an assessment of variation between standardised effect sizes for such risk factors across care outcomes and patient cohorts. Such an approach will support development of more rigorous risk stratification tools and better targeting of intervention measures.

Methods

Data was extracted from the electronic health record of a major tertiary referral centre, over a 3-year period, for all patients discharged from hospital with a concurrent diagnosis of diabetes mellitus. Risk factors selected for extraction were pre-specified according to a systematic review of the research literature. Standardised effect sizes were calculated for all statistically significant risk factors, and compared across patient cohorts and both readmission & mortality outcome measures.

Results

Data was extracted for 46,357 distinct admissions patients, creating a large dataset of approximately 10,281,400 data points. The calculation of standardized effect size measures allowed direct comparison. Effect sizes were noted to be larger for mortality compared to readmission, as well as for being larger for surgical and type 1 diabetes cohorts of patients.

Conclusions

The calculation of standardised effect sizes is an important step in evaluating risk factors for healthcare events. This will improve our understanding of risk and support the development of more effective risk stratification tools to support patients to make better informed decisions at discharge from hospital.",,doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render -35607618,https://doi.org/10.1016/j.patter.2022.100471,"Relevance, redundancy, and complementarity trade-off (RRCT): A principled, generic, robust feature-selection tool.",Tsanas A.,,"Patterns (New York, N.Y.)",2022,2022-03-31,Y,Information theory; Variable selection; Feature Selection; Statistical Learning; Dimensionality Reduction; Curse Of Dimensionality; Principle Of Parsimony,,,"We present a new heuristic feature-selection (FS) algorithm that integrates in a principled algorithmic framework the three key FS components: relevance, redundancy, and complementarity. Thus, we call it relevance, redundancy, and complementarity trade-off (RRCT). The association strength between each feature and the response and between feature pairs is quantified via an information theoretic transformation of rank correlation coefficients, and the feature complementarity is quantified using partial correlation coefficients. We empirically benchmark the performance of RRCT against 19 FS algorithms across four synthetic and eight real-world datasets in indicative challenging settings evaluating the following: (1) matching the true feature set and (2) out-of-sample performance in binary and multi-class classification problems when presenting selected features into a random forest. RRCT is very competitive in both tasks, and we tentatively make suggestions on the generalizability and application of the best-performing FS algorithms across settings where they may operate effectively.",,doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render 32990744,https://doi.org/10.1093/gigascience/giaa095,An extensible big data software architecture managing a research resource of real-world clinical radiology data linked to other health data from the whole Scottish population.,"Nind T, Sutherland J, McAllister G, Hardy D, Hume A, MacLeod R, Caldwell J, Krueger S, Tramma L, Teviotdale R, Abdelatif M, Gillen K, Ward J, Scobbie D, Baillie I, Brooks A, Prodan B, Kerr W, Sloan-Murphy D, Herrera JFR, McManus D, Morris C, Sinclair C, Baxter R, Parsons M, Morris A, Jefferson E.",,GigaScience,2020,2020-09-01,Y,ML; AI; Radiology; Big Data,,,"

Aim

To enable a world-leading research dataset of routinely collected clinical images linked to other routinely collected data from the whole Scottish national population. This includes more than 30 million different radiological examinations from a population of 5.4 million and >2 PB of data collected since 2010.

Methods

Scotland has a central archive of radiological data used to directly provide clinical care to patients. We have developed an architecture and platform to securely extract a copy of those data, link it to other clinical or social datasets, remove personal data to protect privacy, and make the resulting data available to researchers in a controlled Safe Haven environment.

Results

An extensive software platform has been developed to host, extract, and link data from cohorts to answer research questions. The platform has been tested on 5 different test cases and is currently being further enhanced to support 3 exemplar research projects.

Conclusions

The data available are from a range of radiological modalities and scanner types and were collected under different environmental conditions. These real-world, heterogenous data are valuable for training algorithms to support clinical decision making, especially for deep learning where large data volumes are required. The resource is now available for international research access. The platform and data can support new health research using artificial intelligence and machine learning technologies, as well as enabling discovery science.",,doi:https://doi.org/10.1093/gigascience/giaa095; html:https://europepmc.org/articles/PMC7523405; pdf:https://europepmc.org/articles/PMC7523405?pdf=render +35607618,https://doi.org/10.1016/j.patter.2022.100471,"Relevance, redundancy, and complementarity trade-off (RRCT): A principled, generic, robust feature-selection tool.",Tsanas A.,,"Patterns (New York, N.Y.)",2022,2022-03-31,Y,Information theory; Variable selection; Feature Selection; Statistical Learning; Dimensionality Reduction; Curse Of Dimensionality; Principle Of Parsimony,,,"We present a new heuristic feature-selection (FS) algorithm that integrates in a principled algorithmic framework the three key FS components: relevance, redundancy, and complementarity. Thus, we call it relevance, redundancy, and complementarity trade-off (RRCT). The association strength between each feature and the response and between feature pairs is quantified via an information theoretic transformation of rank correlation coefficients, and the feature complementarity is quantified using partial correlation coefficients. We empirically benchmark the performance of RRCT against 19 FS algorithms across four synthetic and eight real-world datasets in indicative challenging settings evaluating the following: (1) matching the true feature set and (2) out-of-sample performance in binary and multi-class classification problems when presenting selected features into a random forest. RRCT is very competitive in both tasks, and we tentatively make suggestions on the generalizability and application of the best-performing FS algorithms across settings where they may operate effectively.",,doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render 37068964,https://doi.org/10.3399/bjgp.2022.0301,OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic.,"Curtis HJ, MacKenna B, Wiedemann M, Fisher L, Croker R, Morton CE, Inglesby P, Walker AJ, Morley J, Mehrkar A, Bacon SC, Hickman G, Evans D, Ward T, Davy S, Hulme WJ, Macdonald O, Conibere R, Lewis T, Myers M, Wanninayake S, Collison K, Drury C, Samuel M, Sood H, Cipriani A, Fazel S, Sharma M, Baqir W, Bates C, Parry J, Goldacre B, OpenSAFELY Collaborative.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-04-27,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19,,,"

Background

The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible.

Aim

To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication.

Design and setting

With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY.

Method

Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month.

Results

Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019).

Conclusion

Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.",,doi:https://doi.org/10.3399/BJGP.2022.0301; html:https://europepmc.org/articles/PMC10131234; pdf:https://europepmc.org/articles/PMC10131234?pdf=render 36193673,https://doi.org/10.1192/j.eurpsy.2022.2324,Cardiac surgery receipt and outcomes for people using secondary mental healthcare services: Retrospective cohort study using a large mental healthcare database in South London.,"Brooks G, Weerakkody R, Harris M, Harris M, Stewart R, Perera G.",,European psychiatry : the journal of the Association of European Psychiatrists,2022,2022-10-04,Y,Cardiac surgery; Length Of Stay; Emergency Admissions; Mental Healthcare Services,,,"

Background

Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery.

Methods

We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission.

Results

Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission.

Conclusion

People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.",,doi:https://doi.org/10.1192/j.eurpsy.2022.2324; html:https://europepmc.org/articles/PMC9677442; pdf:https://europepmc.org/articles/PMC9677442?pdf=render 37311808,https://doi.org/10.1038/s41467-023-39193-y,"Natural history of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-06-13,Y,,,,"Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.",,doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render 34862222,https://doi.org/10.7861/clinmed.2021-0386,'What is the risk to me from COVID-19?': Public involvement in providing mortality risk information for people with 'high-risk' conditions for COVID-19 (OurRisk.CoV).,"Banerjee A, Pasea L, Manohar S, Lai AG, Hemingway E, Sofer I, Katsoulis M, Sood H, Morris A, Cake C, Fitzpatrick NK, Williams B, Denaxas S, Hemingway H, and members of the Health Data Research UK COVID-19 Patient and Public Involvement and Engagement Panel.",,"Clinical medicine (London, England)",2021,2021-11-01,N,Mortality; Coronavirus; Patient And Public Involvement; Risk Information,,,"Patients and public have sought mortality risk information throughout the pandemic, but their needs may not be served by current risk prediction tools. Our mixed methods study involved: (1) systematic review of published risk tools for prognosis, (2) provision and patient testing of new mortality risk estimates for people with high-risk conditions and (3) iterative patient and public involvement and engagement with qualitative analysis. Only one of 53 (2%) previously published risk tools involved patients or the public, while 11/53 (21%) had publicly accessible portals, but all for use by clinicians and researchers.Among people with a wide range of underlying conditions, there has been sustained interest and engagement in accessible and tailored, pre- and postpandemic mortality information. Informed by patient feedback, we provide such information in 'five clicks' (https://covid19-phenomics.org/OurRiskCoV.html), as context for decision making and discussions with health professionals and family members. Further development requires curation and regular updating of NHS data and wider patient and public engagement.",,doi:https://doi.org/10.7861/clinmed.2021-0386; html:https://europepmc.org/articles/PMC8806292; pdf:https://europepmc.org/articles/PMC8806292?pdf=render; doi:https://doi.org/10.7861/clinmed.2021-0386 33079204,https://doi.org/10.1093/ehjqcco/qcaa079,Impact of COVID-19 on cardiac procedure activity in England and associated 30-day mortality.,"Mohamed MO, Banerjee A, Clarke S, de Belder M, Patwala A, Goodwin AT, Kwok CS, Rashid M, Gale CP, Curzen N, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2021,2021-05-01,Y,Mortality; Cardiac; England; Procedures; Covid-19,,,"

Aims

Limited data exist on the impact of COVID-19 on national changes in cardiac procedure activity, including patient characteristics and clinical outcomes before and during the COVID-19 pandemic.

Methods and results

All major cardiac procedures (n = 374 899) performed between 1 January and 31 May for the years 2018, 2019, and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression was performed to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period. Overall, there was a deficit of 45 501 procedures during the COVID period compared to the monthly averages (March-May) in 2018-2019. Cardiac catheterization and device implantations were the most affected in terms of numbers (n = 19 637 and n = 10 453), whereas surgical procedures such as mitral valve replacement, other valve replacement/repair, atrioseptal defect/ventriculoseptal defect repair, and coronary artery bypass grafting were the most affected as a relative percentage difference (Δ) to previous years' averages. Transcatheter aortic valve replacement was the least affected (Δ -10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterization [OR 1.25 95% confidence interval (CI) 1.07-1.47, P = 0.006] and cardiac device implantation (OR 1.35 95% CI 1.15-1.58, P < 0.001).

Conclusion

Cardiac procedural activity has significantly declined across England during the COVID-19 pandemic, with a deficit in excess of 45 000 procedures, without an increase in risk of mortality for most cardiac procedures performed during the pandemic. Major restructuring of cardiac services is necessary to deal with this deficit, which would inevitably impact long-term morbidity and mortality.",,doi:https://doi.org/10.1093/ehjqcco/qcaa079; html:https://europepmc.org/articles/PMC7665465; pdf:https://europepmc.org/articles/PMC7665465?pdf=render -33948220,https://doi.org/10.1177/20552076211007661,Association between glycosylated haemoglobin and outcomes for patients discharged from hospital with diabetes: A health informatics approach.,"Robbins T, Sankaranarayanan S, Randeva H, Keung SNLC, Arvanitis TN.",,Digital health,2021,2021-01-01,Y,Biochemistry; Diabetes; Hospital Discharge; Readmission; Health Informatics,,,"

Aims/objectives

Extensive research considers associations between inpatient glycaemic control and outcomes during hospital admission; this cautions against overly tight glycaemic targets. Little research considers glycaemic control following hospital discharge. This is despite a clear understanding that people with diabetes are at increased risk of negative outcomes, following discharge. We evaluate absolute and relative Hba1c values, and frequency of Hba1c monitoring, on readmission and mortality rates for people discharged from hospital with diabetes.

Methods

All discharges (n = 46,357) with diabetes from a major tertiary referral centre over 3 years were extracted, including biochemistry data. We conducted an evaluation of association between Hba1c, mortality and readmission, statistical significance and standardised Cohen's D effect size calculations.

Results

399 patients had a Hba1c performed during their admission. 3,138 patients had a Hba1c within 1 year of discharge. Mean average Hba1c for readmissions was 57.82 vs 60.39 for not readmitted (p = 0.009, Cohen's D 0.28). Mean average number of days to Hba1c testing in readmitted was 97 vs 113 for those not readmitted (p = 0.00006, Cohen's D 0.39). Further evaluation of mortality outcomes, cohorts of T1DM and T2DM and association of relative change in Hba1c was performed.

Conclusions

Lower Hba1c values following discharge from hospital are significantly associated with increased risk of readmission, as is a shorter duration until testing. Similar patterns observed for mortality. Findings particularly prominent for T1DM. Further research needed to consider underlying causation and design of appropriate risk stratification models.",,doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render 36755846,https://doi.org/10.1093/ckj/sfac241,"Depression is associated with frailty and lower quality of life in haemodialysis recipients, but not with mortality or hospitalization.","Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,Clinical kidney journal,2023,2022-10-31,Y,Mortality; Depression; Frailty; Haemodialysis; Hospitalization; Health-related Quality Of Life,,,"

Background

Frailty and depression are highly prevalent in haemodialysis recipients, exhibit a reciprocal relationship, and are associated with increased mortality and hospitalization, and lower quality of life. Despite this, there has been little exploration of the relationship between depression and frailty upon patient outcomes. We aimed to explore the relationship between depression and frailty, and their associations with mortality, hospitalization and quality of life.

Methods

We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalization. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), frailty using the Clinical Frailty Scale (CFS) and quality of life using the EuroQol 5-Dimension (EQ-5D) Summary Index.

Results

A total of 485 prevalent haemodialysis recipients were recruited, with 111 deaths and 1241 hospitalizations during follow-up. CFS was independently associated with mortality [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.08, 1.59; P = .006], hospitalization [incidence rate ratio (IRR) 1.13; 95% CI 1.03, 1.25; P = .010] and lower quality of life (Coef. -0.401; 95% CI -0.511, -0.292; P < .001). PHQ-9 score was independently associated with lower quality of life (Coef. -0.042; 95% CI -0.063, -0.021; P < .001), but not mortality (HR 1.00; 95% CI 0.96, 1.04; P = .901) or hospitalization (IRR 0.99; 95% CI 0.97, 1.01; P = .351). In an adjusted model including CFS, moderate depression was associated with reduced hospitalization (IRR 0.72; 95% CI 0.56, 0.93; P = .013).

Conclusions

With the addition of frailty, depression was associated with lower hospital admissions, but poorer quality of life. The relationship between frailty and depression, and their influence on outcomes is complex, requiring further study.",,doi:https://doi.org/10.1093/ckj/sfac241; html:https://europepmc.org/articles/PMC9900564; pdf:https://europepmc.org/articles/PMC9900564?pdf=render -37408471,https://doi.org/10.1093/eurheartj/ehad424,The CODE-EHR global framework: lifting the veil on health record data.,"Asselbergs FW, Kotecha D.",,European heart journal,2023,2023-07-06,N,,,,,,doi:https://doi.org/10.1093/eurheartj/ehad424 -36536453,https://doi.org/10.1186/s41512-022-00137-7,Protocol for development and validation of postpartum cardiovascular disease (CVD) risk prediction model incorporating reproductive and pregnancy-related candidate predictors.,"Wambua S, Crowe F, Thangaratinam S, O'Reilly D, McCowan C, Brophy S, Yau C, Nirantharakumar K, Riley R, MuM-PreDiCT Group.",,Diagnostic and prognostic research,2022,2022-12-19,Y,Prognosis; Cardiovascular disease; Pregnant women; Pregnancy complications; Prediction Modeling,,,"

Background

Cardiovascular disease (CVD) is a leading cause of death among women. CVD is associated with reduced quality of life, significant treatment and management costs, and lost productivity. Estimating the risk of CVD would help patients at a higher risk of CVD to initiate preventive measures to reduce risk of disease. The Framingham risk score and the QRISK® score are two risk prediction models used to evaluate future CVD risk in the UK. Although the algorithms perform well in the general population, they do not take into account pregnancy complications, which are well known risk factors for CVD in women and have been highlighted in a recent umbrella review. We plan to develop a robust CVD risk prediction model to assess the additional value of pregnancy risk factors in risk prediction of CVD in women postpartum.

Methods

Using candidate predictors from QRISK®-3, the umbrella review identified from literature and from discussions with clinical experts and patient research partners, we will use time-to-event Cox proportional hazards models to develop and validate a 10-year risk prediction model for CVD postpartum using Clinical Practice Research Datalink (CPRD) primary care database for development and internal validation of the algorithm and the Secure Anonymised Information Linkage (SAIL) databank for external validation. We will then assess the value of additional candidate predictors to the QRISK®-3 in our internal and external validations.

Discussion

The developed risk prediction model will incorporate pregnancy-related factors which have been shown to be associated with future risk of CVD but have not been taken into account in current risk prediction models. Our study will therefore highlight the importance of incorporating pregnancy-related risk factors into risk prediction modeling for CVD postpartum.",,doi:https://doi.org/10.1186/s41512-022-00137-7; html:https://europepmc.org/articles/PMC9761974; pdf:https://europepmc.org/articles/PMC9761974?pdf=render +33948220,https://doi.org/10.1177/20552076211007661,Association between glycosylated haemoglobin and outcomes for patients discharged from hospital with diabetes: A health informatics approach.,"Robbins T, Sankaranarayanan S, Randeva H, Keung SNLC, Arvanitis TN.",,Digital health,2021,2021-01-01,Y,Biochemistry; Diabetes; Hospital Discharge; Readmission; Health Informatics,,,"

Aims/objectives

Extensive research considers associations between inpatient glycaemic control and outcomes during hospital admission; this cautions against overly tight glycaemic targets. Little research considers glycaemic control following hospital discharge. This is despite a clear understanding that people with diabetes are at increased risk of negative outcomes, following discharge. We evaluate absolute and relative Hba1c values, and frequency of Hba1c monitoring, on readmission and mortality rates for people discharged from hospital with diabetes.

Methods

All discharges (n = 46,357) with diabetes from a major tertiary referral centre over 3 years were extracted, including biochemistry data. We conducted an evaluation of association between Hba1c, mortality and readmission, statistical significance and standardised Cohen's D effect size calculations.

Results

399 patients had a Hba1c performed during their admission. 3,138 patients had a Hba1c within 1 year of discharge. Mean average Hba1c for readmissions was 57.82 vs 60.39 for not readmitted (p = 0.009, Cohen's D 0.28). Mean average number of days to Hba1c testing in readmitted was 97 vs 113 for those not readmitted (p = 0.00006, Cohen's D 0.39). Further evaluation of mortality outcomes, cohorts of T1DM and T2DM and association of relative change in Hba1c was performed.

Conclusions

Lower Hba1c values following discharge from hospital are significantly associated with increased risk of readmission, as is a shorter duration until testing. Similar patterns observed for mortality. Findings particularly prominent for T1DM. Further research needed to consider underlying causation and design of appropriate risk stratification models.",,doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render 34474011,https://doi.org/10.1016/s0140-6736(21)01638-x,Redefining β-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.,"Karwath A, Bunting KV, Gill SK, Tica O, Pendleton S, Aziz F, Barsky AD, Chernbumroong S, Duan J, Mobley AR, Cardoso VR, Slater L, Williams JA, Bruce EJ, Wang X, Flather MD, Coats AJS, Gkoutos GV, Kotecha D, card AIc group and the Beta-blockers in Heart Failure Collaborative Group.",,"Lancet (London, England)",2021,2021-08-30,Y,,,,"

Background

Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation.

Methods

Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β blockers. All-cause mortality during median 1·3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm. The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach. This study was prospectively registered with ClinicalTrials.gov (NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012).

Findings

15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56-72) and LVEF 27% (IQR 21-33). 3708 (24%) patients were women. In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from β blockers, with odds ratios (ORs) ranging from 0·54 to 0·74. One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0·86, 95% CI 0·67-1·10; p=0·22). In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of β blockers versus placebo (OR 0·92, 0·77-1·10; p=0·37). One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with β blockers (OR 0·57, 0·35-0·93; p=0·023). The robustness and consistency of clustering was confirmed for all models (p<0·0001 vs random), and cluster membership was externally validated across the nine independent trials.

Interpretation

An artificial intelligence-based clustering approach was able to distinguish prognostic response from β blockers in patients with heart failure and reduced LVEF. This included patients in sinus rhythm with suboptimal efficacy, as well as a cluster of patients with atrial fibrillation where β blockers did reduce mortality.

Funding

Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.",,doi:https://doi.org/10.1016/S0140-6736(21)01638-X; html:https://europepmc.org/articles/PMC8542730; doi:https://doi.org/10.1016/s0140-6736(21)01638-x +37408471,https://doi.org/10.1093/eurheartj/ehad424,The CODE-EHR global framework: lifting the veil on health record data.,"Asselbergs FW, Kotecha D.",,European heart journal,2023,2023-07-06,N,,,,,,doi:https://doi.org/10.1093/eurheartj/ehad424 34432797,https://doi.org/10.1371/journal.pone.0255748,Regional performance variation in external validation of four prediction models for severity of COVID-19 at hospital admission: An observational multi-centre cohort study.,"Wickstrøm KE, Vitelli V, Carr E, Holten AR, Bendayan R, Reiner AH, Bean D, Searle T, Shek A, Kraljevic Z, Teo J, Dobson R, Tonby K, Köhn-Luque A, Amundsen EK.",,PloS one,2021,2021-08-25,Y,,,,"

Background

Prediction models should be externally validated to assess their performance before implementation. Several prediction models for coronavirus disease-19 (COVID-19) have been published. This observational cohort study aimed to validate published models of severity for hospitalized patients with COVID-19 using clinical and laboratory predictors.

Methods

Prediction models fitting relevant inclusion criteria were chosen for validation. The outcome was either mortality or a composite outcome of mortality and ICU admission (severe disease). 1295 patients admitted with symptoms of COVID-19 at Kings Cross Hospital (KCH) in London, United Kingdom, and 307 patients at Oslo University Hospital (OUH) in Oslo, Norway were included. The performance of the models was assessed in terms of discrimination and calibration.

Results

We identified two models for prediction of mortality (referred to as Xie and Zhang1) and two models for prediction of severe disease (Allenbach and Zhang2). The performance of the models was variable. For prediction of mortality Xie had good discrimination at OUH with an area under the receiver-operating characteristic (AUROC) 0.87 [95% confidence interval (CI) 0.79-0.95] and acceptable discrimination at KCH, AUROC 0.79 [0.76-0.82]. In prediction of severe disease, Allenbach had acceptable discrimination (OUH AUROC 0.81 [0.74-0.88] and KCH AUROC 0.72 [0.68-0.75]). The Zhang models had moderate to poor discrimination. Initial calibration was poor for all models but improved with recalibration.

Conclusions

The performance of the four prediction models was variable. The Xie model had the best discrimination for mortality, while the Allenbach model had acceptable results for prediction of severe disease.",,doi:https://doi.org/10.1371/journal.pone.0255748; html:https://europepmc.org/articles/PMC8386866; pdf:https://europepmc.org/articles/PMC8386866?pdf=render +36536453,https://doi.org/10.1186/s41512-022-00137-7,Protocol for development and validation of postpartum cardiovascular disease (CVD) risk prediction model incorporating reproductive and pregnancy-related candidate predictors.,"Wambua S, Crowe F, Thangaratinam S, O'Reilly D, McCowan C, Brophy S, Yau C, Nirantharakumar K, Riley R, MuM-PreDiCT Group.",,Diagnostic and prognostic research,2022,2022-12-19,Y,Prognosis; Cardiovascular disease; Pregnant women; Pregnancy complications; Prediction Modeling,,,"

Background

Cardiovascular disease (CVD) is a leading cause of death among women. CVD is associated with reduced quality of life, significant treatment and management costs, and lost productivity. Estimating the risk of CVD would help patients at a higher risk of CVD to initiate preventive measures to reduce risk of disease. The Framingham risk score and the QRISK® score are two risk prediction models used to evaluate future CVD risk in the UK. Although the algorithms perform well in the general population, they do not take into account pregnancy complications, which are well known risk factors for CVD in women and have been highlighted in a recent umbrella review. We plan to develop a robust CVD risk prediction model to assess the additional value of pregnancy risk factors in risk prediction of CVD in women postpartum.

Methods

Using candidate predictors from QRISK®-3, the umbrella review identified from literature and from discussions with clinical experts and patient research partners, we will use time-to-event Cox proportional hazards models to develop and validate a 10-year risk prediction model for CVD postpartum using Clinical Practice Research Datalink (CPRD) primary care database for development and internal validation of the algorithm and the Secure Anonymised Information Linkage (SAIL) databank for external validation. We will then assess the value of additional candidate predictors to the QRISK®-3 in our internal and external validations.

Discussion

The developed risk prediction model will incorporate pregnancy-related factors which have been shown to be associated with future risk of CVD but have not been taken into account in current risk prediction models. Our study will therefore highlight the importance of incorporating pregnancy-related risk factors into risk prediction modeling for CVD postpartum.",,doi:https://doi.org/10.1186/s41512-022-00137-7; html:https://europepmc.org/articles/PMC9761974; pdf:https://europepmc.org/articles/PMC9761974?pdf=render 34238721,https://doi.org/10.1016/s2589-7500(21)00105-9,Temporal trends and forecasting of COVID-19 hospitalisations and deaths in Scotland using a national real-time patient-level data platform: a statistical modelling study.,"Simpson CR, Robertson C, Vasileiou E, Moore E, McCowan C, Agrawal U, Stagg HR, Docherty A, Mulholland R, Murray JLK, Ritchie LD, McMenamin J, Sheikh A.",,The Lancet. Digital health,2021,2021-07-05,Y,,,,"

Background

As the COVID-19 pandemic continues, national-level surveillance platforms with real-time individual person-level data are required to monitor and predict the epidemiological and clinical profile of COVID-19 and inform public health policy. We aimed to create a national dataset of patient-level data in Scotland to identify temporal trends and COVID-19 risk factors, and to develop a novel statistical prediction model to forecast COVID-19-related deaths and hospitalisations during the second wave.

Methods

We established a surveillance platform to monitor COVID-19 temporal trends using person-level primary care data (including age, sex, socioeconomic status, urban or rural residence, care home residence, and clinical risk factors) linked to data on SARS-CoV-2 RT-PCR tests, hospitalisations, and deaths for all individuals resident in Scotland who were registered with a general practice on Feb 23, 2020. A Cox proportional hazards model was used to estimate the association between clinical risk groups and time to hospitalisation and death. A survival prediction model derived from data from March 1 to June 23, 2020, was created to forecast hospital admissions and deaths from October to December, 2020. We fitted a generalised additive spline model to daily SARS-CoV-2 cases over the previous 10 weeks and used this to create a 28-day forecast of the number of daily cases. The age and risk group pattern of cases in the previous 3 weeks was then used to select a stratified sample of individuals from our cohort who had not previously tested positive, with future cases in each group sampled from a multinomial distribution. We then used their patient characteristics (including age, sex, comorbidities, and socioeconomic status) to predict their probability of hospitalisation or death.

Findings

Our cohort included 5 384 819 people, representing 98·6% of the entire estimated population residing in Scotland during 2020. Hospitalisation and death among those testing positive for SARS-CoV-2 between March 1 and June 23, 2020, were associated with several patient characteristics, including male sex (hospitalisation hazard ratio [HR] 1·47, 95% CI 1·38-1·57; death HR 1·62, 1·49-1·76) and various comorbidities, with the highest hospitalisation HR found for transplantation (4·53, 1·87-10·98) and the highest death HR for myoneural disease (2·33, 1·46-3·71). For those testing positive, there were decreasing temporal trends in hospitalisation and death rates. The proportion of positive tests among older age groups (>40 years) and those with at-risk comorbidities increased during October, 2020. On Nov 10, 2020, the projected number of hospitalisations for Dec 8, 2020 (28 days later) was 90 per day (95% prediction interval 55-125) and the projected number of deaths was 21 per day (12-29).

Interpretation

The estimated incidence of SARS-CoV-2 infection based on positive tests recorded in this unique data resource has provided forecasts of hospitalisation and death rates for the whole of Scotland. These findings were used by the Scottish Government to inform their response to reduce COVID-19-related morbidity and mortality.

Funding

Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, UK Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Scottish Government Director General Health and Social Care.",,doi:https://doi.org/10.1016/S2589-7500(21)00105-9; html:https://europepmc.org/articles/PMC8257056 34582457,https://doi.org/10.1371/journal.pmed.1003777,Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.,"Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau-Hyam M, Elliott P.",,PLoS medicine,2021,2021-09-28,Y,,,,"

Background

Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type.

Methods and findings

We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England.

Conclusions

Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.",,doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?pdf=render 36145196,https://doi.org/10.3390/nu14183821,Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial.,"Jolliffe DA, Vivaldi G, Chambers ES, Cai W, Li W, Faustini SE, Gibbons JM, Pade C, Coussens AK, Richter AG, McKnight Á, Martineau AR.",,Nutrients,2022,2022-09-16,Y,Interferon gamma; Vitamin D; Antibody; Randomised Controlled Trial; Breakthrough Sars-cov-2 Infection; Bnt162b2 Pfizer; Chadox1 Ncov-19 Oxford–astrazeneca,,,"Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford−AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8−34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1−58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.",,doi:https://doi.org/10.3390/nu14183821; html:https://europepmc.org/articles/PMC9506404; pdf:https://europepmc.org/articles/PMC9506404?pdf=render @@ -329,12 +330,12 @@ PMC10464868,https://doi.org/,An overview of synthetic administrative data for re 37340508,https://doi.org/10.1186/s13059-023-02983-0,CNETML: maximum likelihood inference of phylogeny from copy number profiles of multiple samples.,"Lu B, Curtius K, Graham TA, Yang Z, Barnes CP.",,Genome biology,2023,2023-06-20,Y,Maximum likelihood; Copy Number Alteration; Phylogeny Inference; Low-coverage Sequencing; Model Of Evolution,,,"Phylogenetic trees based on copy number profiles from multiple samples of a patient are helpful to understand cancer evolution. Here, we develop a new maximum likelihood method, CNETML, to infer phylogenies from such data. CNETML is the first program to jointly infer the tree topology, node ages, and mutation rates from total copy numbers of longitudinal samples. Our extensive simulations suggest CNETML performs well on copy numbers relative to ploidy and under slight violation of model assumptions. The application of CNETML to real data generates results consistent with previous discoveries and provides novel early copy number events for further investigation.",,doi:https://doi.org/10.1186/s13059-023-02983-0; html:https://europepmc.org/articles/PMC10283241; pdf:https://europepmc.org/articles/PMC10283241?pdf=render 35671273,https://doi.org/10.1371/journal.pone.0268837,Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England.,"Onen-Dumlu Z, Harper AL, Forte PG, Powell AL, Pitt M, Vasilakis C, Wood RM.",,PloS one,2022,2022-06-07,Y,,,,"

Objectives

While there has been significant research on the pressures facing acute hospitals during the COVID-19 pandemic, there has been less interest in downstream community services which have also been challenged in meeting demand. This study aimed to estimate the theoretical cost-optimal capacity requirement for 'step down' intermediate care services within a major healthcare system in England, at a time when considerable uncertainty remained regarding vaccination uptake and the easing of societal restrictions.

Methods

Demand for intermediate care was projected using an epidemiological model (for COVID-19 demand) and regressing upon public mobility (for non-COVID-19 demand). These were inputted to a computer simulation model of patient flow from acute discharge readiness to bedded and home-based Discharge to Assess (D2A) intermediate care services. Cost-optimal capacity was defined as that which yielded the lowest total cost of intermediate care provision and corresponding acute discharge delays.

Results

Increased intermediate care capacity is likely to bring about lower system-level costs, with the additional D2A investment more than offset by substantial reductions in costly acute discharge delays (leading also to improved patient outcome and experience). Results suggest that completely eliminating acute 'bed blocking' is unlikely economical (requiring large amounts of downstream capacity), and that health systems should instead target an appropriate tolerance based upon the specific characteristics of the pathway.

Conclusions

Computer modelling can be a valuable asset for determining optimal capacity allocation along the complex care pathway. With results supporting a Business Case for increased downstream capacity, this study demonstrates how modelling can be applied in practice and provides a blueprint for use alongside the freely-available model code.",,doi:https://doi.org/10.1371/journal.pone.0268837; html:https://europepmc.org/articles/PMC9173611; pdf:https://europepmc.org/articles/PMC9173611?pdf=render 34232969,https://doi.org/10.23889/ijpds.v5i1.1151,How effective are population health surveys for estimating prevalence of chronic conditions compared to anonymised clinical data?,"Whiffen T, Akbari A, Paget T, Lowe S, Lyons R.",,International journal of population data science,2020,2020-06-12,Y,,,,"

Introduction

Population health surveys are used to record person-reported outcome measures for chronic health conditions and provide a useful source of data when evaluating potential disease burdens. The reliability of survey-based prevalence estimates for chronic diseases is unclear nonetheless. This study applied methodological triangulation via a data linkage method to validate prevalence of selected chronic conditions (angina, myocardial infarction, heart failure, and asthma).

Methods

Linked healthcare records were used for a combined cohort of 11,323 adults from the 2013 and 2014 sweeps of the Welsh Health Survey (WHS). The approach utilised consented survey data linked to primary and secondary care electronic health record (EHR) data back to 2002 within the Secure Anonymised Information Linkage (SAIL) Databank.

Results

This descriptive study demonstrates validation of survey and clinical data using data linkage for selected chronic cardiovascular conditions and asthma with varied success. The results indicate that identifying cases for separate cardiovascular conditions was limited without specific medication codes for each condition, but more straightforward for asthma, where there was an extensive list of medications available. For asthma there was better agreement between prevalence estimates based on survey and clinical data as a result.

Conclusion

Whilst the results provide external validity for the WHS as an instrument for estimating the burden of chronic disease, they also indicate that a data linkage appproach can be used to produce comparable prevalence estimates using clinical data if a defined condition-specific set of clinical codes are available.",,doi:https://doi.org/10.23889/ijpds.v5i1.1151; html:https://europepmc.org/articles/PMC7473295; pdf:https://europepmc.org/articles/PMC7473295?pdf=render -36691170,https://doi.org/10.1136/bmjopen-2022-061344,"Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK.","Marchant E, Lowthian E, Crick T, Griffiths LJ, Fry R, Dadaczynski K, Okan O, James M, Cowley L, Torabi F, Kennedy J, Akbari A, Lyons R, Brophy S.",,BMJ open,2022,2022-09-07,Y,epidemiology; Public Health; Community Child Health; Covid-19,,,"

Objectives

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

Design

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

Setting

Children attending primary schools in Wales (2018-2020), UK, who were part of the Health and Attainment of Pupils in a Primary Education Network (HAPPEN)_school network.

Participants

Complete linked records of eligible participants were obtained for n=7062 individuals. 39.1% (n=2764) were tested (age 10.6±0.9; 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0; 54.5% girls).

Main outcome measures

Logistic regression of health-related behaviours and demographics were used to determine the ORs of factors associated with (1) being tested for SARS-CoV-2 and (2) testing positive for SARS-CoV-2.

Results

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

Conclusions

Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include coparticipation with others and exposure to SARS-CoV-2. A risk-versus-benefit approach must be considered in relation to promoting these health behaviours, given the importance of health-related behaviours such as childhood physical activity for development.",,doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?pdf=render +36691170,https://doi.org/10.1136/bmjopen-2022-061344,"Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK.","Marchant E, Lowthian E, Crick T, Griffiths LJ, Fry R, Dadaczynski K, Okan O, James M, Cowley L, Torabi F, Kennedy J, Akbari A, Lyons R, Brophy S.",,BMJ open,2022,2022-09-07,Y,epidemiology; Public Health; Community Child Health; Covid-19,,,"

Objectives

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

Design

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

Setting

Children attending primary schools in Wales (2018-2020), UK, who were part of the Health and Attainment of Pupils in a Primary Education Network (HAPPEN)_school network.

Participants

Complete linked records of eligible participants were obtained for n=7062 individuals. 39.1% (n=2764) were tested (age 10.6±0.9; 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0; 54.5% girls).

Main outcome measures

Logistic regression of health-related behaviours and demographics were used to determine the ORs of factors associated with (1) being tested for SARS-CoV-2 and (2) testing positive for SARS-CoV-2.

Results

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

Conclusions

Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include coparticipation with others and exposure to SARS-CoV-2. A risk-versus-benefit approach must be considered in relation to promoting these health behaviours, given the importance of health-related behaviours such as childhood physical activity for development.",,doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e061344.full.pdf 35922409,https://doi.org/10.1038/s41467-022-32121-6,Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England.,"Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby J, Haw D, Elliott J, Whitaker M, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CA.",,Nature communications,2022,2022-08-03,Y,,,,"Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n = 102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R = 0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R = 1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.",,doi:https://doi.org/10.1038/s41467-022-32121-6; html:https://europepmc.org/articles/PMC9349208; pdf:https://europepmc.org/articles/PMC9349208?pdf=render 35361119,https://doi.org/10.1186/s12859-022-04641-x,classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes.,"Quinn GP, Sessler T, Ahmaderaghi B, Lambe S, VanSteenhouse H, Lawler M, Wappett M, Seligmann B, Longley DB, McDade SS.",,BMC bioinformatics,2022,2022-03-31,Y,Gene Expression; Functional Annotation; Cancer Subtype; Shiny Application; Colorectal Shiny Cms Cris Immune,,,"

Background

Transcriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five intrinsic (CRIS) sub-types that have prognostic and predictive value. Breast cancer (BRCA) has five PAM50 molecular subgroups with similar value, and the OncotypeDX test provides transcriptomic based clinically actionable treatment-risk stratification. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time consuming and requires significant bioinformatics experience. There is no ""universal"" method of using data from diverse assay/sequencing platforms to provide subgroup classification using the established classifier sets of genes (CMS, CRIS, PAM50, OncotypeDX), nor one which in provides additional useful functional annotations such as cellular composition, single-sample Gene Set Enrichment Analysis, or prediction of transcription factor activity.

Results

To address this bottleneck, we developed classifieR, an easy-to-use R-Shiny based web application that supports flexible rapid single sample annotation of transcriptional profiles derived from cancer patient samples form diverse platforms. We demonstrate the utility of the "" classifieR"" framework to applications focused on the analysis of transcriptional profiles from colorectal (classifieRc) and breast (classifieRb). Samples are annotated with disease relevant transcriptional subgroups (CMS/CRIS sub-types in classifieRc and PAM50/inferred OncotypeDX in classifieRb), estimation of cellular composition using MCP-counter and xCell, single-sample Gene Set Enrichment Analysis (ssGSEA) and transcription factor activity predictions with Discriminant Regulon Expression Analysis (DoRothEA).

Conclusions

classifieR provides a framework which enables labs without access to a dedicated bioinformation can get information on the molecular makeup of their samples, providing an insight into patient prognosis, druggability and also as a tool for analysis and discovery. Applications are hosted online at https://generatr.qub.ac.uk/app/classifieRc and https://generatr.qub.ac.uk/app/classifieRb after signing up for an account on https://generatr.qub.ac.uk .",,doi:https://doi.org/10.1186/s12859-022-04641-x; html:https://europepmc.org/articles/PMC8974006; pdf:https://europepmc.org/articles/PMC8974006?pdf=render 35909578,https://doi.org/10.23889/ijpds.v7i1.1717,"Health and household environment factors linked with early alcohol use in adolescence: a record-linked, data-driven, longitudinal cohort study.","Bandyopadhyay A, Brophy S, Akbari A, Demmler J, Kennedy J, Paranjothy S, Lyons RA, Moore S.",,International journal of population data science,2022,2022-07-07,Y,Alcohol; Adolescent; Cohort study; Data Linkage; Electronic Health Records (Ehrs),,,"

Introduction

Early alcohol use has significant association with poor health outcomes. Individual risk factors around early alcohol use have been identified, but a holistic, data-driven investigation into health and household environmental factors on early alcohol use is yet to be undertaken.

Objectives

This study aims to investigate the relationship between preceding health events, household exposures and early alcohol use during adolescence using a two-stage data-driven approach.

Methods

In stage one, a study population (N = 1,072) were derived from the Millennium Cohort Study (MCS) Wales (born between 2000-2002). MCS data were first linked with electronic-health records. Factors associated with early (<=eleven years old) alcohol use were identified using feature selection and stepwise logistic regression. In stage two, analogous risk factors from MCS were recreated for whole population (N = 59,231) of children (born between 1998-2002 in the Welsh Demographic Service Dataset) using routine data to predict the alcohol-related health events in hospital or GP records.

Results

Significant risk factors from stage two included poor maternal mental (adjusted odds ratio [aOR] = 1.31) and physical health (aOR = 1.25), living with someone with alcohol-related problem (aOR = 2.16), single-adult household (aOR = 1.45), ever in deprivation (aOR = 1.66), child's high hyperactivity (aOR = 3.57), and conduct disorder (aOR = 3.26). Children with health events, whose health needs are supported (e.g., are taken to the doctor), are at lower risk of early alcohol use.

Conclusion

Health events of the family members and the child can act as modifiable exposures and may therefore inform the development of prevention initiatives. Families with known alcohol problems, living in deprivation, experiencing child behavioural problems and those who are not taken to the doctor are at higher risk of early drinking behaviour and should be prioritised for early years support and interventions to target problem drinking in young people.",,doi:https://doi.org/10.23889/ijpds.v7i1.1717; html:https://europepmc.org/articles/PMC9284510; pdf:https://europepmc.org/articles/PMC9284510?pdf=render; pdf:https://ijpds.org/article/download/1717/3510 -36863848,https://doi.org/10.1136/archdischild-2022-325152,Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.,"Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.",,Archives of disease in childhood,2023,2023-03-02,Y,epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19,,,"

Objective

To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.

Design

Serial cross-sectional study.

Setting

Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).

Study population

Children aged 5-17 years in the community.

Predictors

Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.

Main outcome measures

Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19.

Results

Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.

Conclusions

One in 23 5-11 year-olds and one in eight 12-17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities.",,doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render 34461893,https://doi.org/10.1186/s12916-021-02096-0,The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.,"Wilde H, Mellan T, Hawryluk I, Dennis JM, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer SJ.",,BMC medicine,2021,2021-08-30,Y,Critical Care; Hospital Mortality; Quality Of Healthcare; Public Health Surveillance; Coronavirus Infection,,,"

Background

The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.

Methods

A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).

Results

One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].

Conclusion

Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.",,doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render +36863848,https://doi.org/10.1136/archdischild-2022-325152,Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.,"Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.",,Archives of disease in childhood,2023,2023-03-02,Y,epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19,,,"

Objective

To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.

Design

Serial cross-sectional study.

Setting

Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).

Study population

Children aged 5-17 years in the community.

Predictors

Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.

Main outcome measures

Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19.

Results

Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.

Conclusions

One in 23 5-11 year-olds and one in eight 12-17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities.",,doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render PMC10464864,https://doi.org/,Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study),"Walshe J, Akbari A, Hawthorne A, Laing H.",,International journal of population data science,,2023-08-31,Y,"Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care",,,"Abstract

Introduction

Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.

Objectives

Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies (“biologics”) in a single, publicly funded, healthcare system.

Results

We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.

Conclusions

We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464864/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464864/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?pdf=render 36481043,https://doi.org/10.1016/s2468-1253(22)00389-2,Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.,"Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald TJ, Lamb CA, Sebastian S, Kok K, Lees CW, Hart AL, Pollok RC, Boyton RJ, Altmann DM, Pollock KM, Goodhand JR, Kennedy NA, Ahmad T, Powell N, CLARITY study investigators.",,The lancet. Gastroenterology & hepatology,2023,2022-12-05,Y,,,,"

Background

Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection.

Methods

CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual.

Findings

Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028).

Interpretation

Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies.

Funding

Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos.",,doi:https://doi.org/10.1016/S2468-1253(22)00389-2; html:https://europepmc.org/articles/PMC9757903; pdf:https://europepmc.org/articles/PMC9757903?pdf=render; doi:https://doi.org/10.1016/s2468-1253(22)00389-2 32946449,https://doi.org/10.1371/journal.pone.0237676,"Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.","Cooksey R, Kennedy J, Dennis MS, Escott-Price V, Lyons RA, Seaborne M, Brophy S.",,PloS one,2020,2020-09-18,Y,,,,"

Objectives

Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia.

Methods and findings

A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders. The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p<0.01).

Conclusions

This study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk. Previously reported links may be associated with confounders of people using PPI's, such as increased risk of cardiovascular disease and/or depression and their associated medications which may be responsible for any increased risk of developing dementia.",,doi:https://doi.org/10.1371/journal.pone.0237676; html:https://europepmc.org/articles/PMC7500586; pdf:https://europepmc.org/articles/PMC7500586?pdf=render @@ -350,8 +351,8 @@ PMC10464864,https://doi.org/,Data linkage can reduce the burden and increase the 35173150,https://doi.org/10.1038/s41467-022-28527-x,"Population antibody responses following COVID-19 vaccination in 212,102 individuals.","Ward H, Whitaker M, Flower B, Tang SN, Atchison C, Darzi A, Donnelly CA, Cann A, Diggle PJ, Ashby D, Riley S, Barclay WS, Elliott P, Cooke GS.",,Nature communications,2022,2022-02-16,Y,,,,"Population antibody surveillance helps track immune responses to COVID-19 vaccinations at scale, and identify host factors that may affect antibody production. We analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1. For both vaccines, antibody positivity peaks 4-5 weeks after first dose and then declines. At least 21 days after second dose of BNT162b2, close to 100% of respondents test positive, while for ChAdOx1, this is significantly reduced, particularly in the oldest age groups (72.7% [70.9-74.4] at ages 75 years and above). For both vaccines, antibody positivity decreases with age, and is higher in females and those with previous infection. Antibody positivity is lower in transplant recipients, obese individuals, smokers and those with specific comorbidities. These groups will benefit from additional vaccine doses.",,doi:https://doi.org/10.1038/s41467-022-28527-x; html:https://europepmc.org/articles/PMC8850615; pdf:https://europepmc.org/articles/PMC8850615?pdf=render 37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"

Purpose

People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.

Methods

We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.

Results

There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.

Conclusions

COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render 35197134,https://doi.org/10.1192/bjo.2022.24,Birth without intervention in women with severe mental illness: cohort study.,"Taylor C, Stewart R, Gibson R, Pasupathy D, Shetty H, Howard L.",,BJPsych open,2022,2022-02-24,Y,Schizophrenia; epidemiology; Perinatal Psychiatry; Bipolar Affective Disorders; Birth Without Intervention,,,"

Summary

The rate of normal birth outcomes (i.e. full-term births without intervention) for women with severe mental illness (SMI - psychotic and bipolar disorders) is not known. We examined rates of birth without intervention (spontaneous labour onset, spontaneous vaginal delivery without instruments, no episiotomy and no indication of pre- or post-delivery anaesthesia) in women with SMI (584 pregnancies) compared with a control population (70 942 pregnancies). Outcome ratios were calculated standardising for age. Women with SMI were less likely to have a birth without intervention (29.5%) relative to the control population (36.8%) (standardised outcome ratio 0.74, 95% CI 0.63-0.87).",,doi:https://doi.org/10.1192/bjo.2022.24; html:https://europepmc.org/articles/PMC8935938; pdf:https://europepmc.org/articles/PMC8935938?pdf=render -33240522,https://doi.org/10.1177/2055207620965046,Electronic-prescribing tools improve N-acetylcysteine prescription accuracy and timeliness for patients who present following a paracetamol overdose: A digital innovation quality-improvement project.,"McCulloch A, Sarwar A, Bate T, Thompson D, McDowell P, Sharif Q, Sapey E, Seccombe A.",,Digital health,2020,2020-01-01,Y,Antidote; Digital; paracetamol; Prescription Errors; Electronic Health Systems,,,"

Objectives

Prescription error rates and delays in treatment provision are high for N-acetylcysteine (NAC) when prescribed for paracetamol overdose (POD). We hypothesised that an electronic tool which proposed the complete NAC regimen would reduce prescription errors and improve the timeliness of NAC provision. Error rates and delays in the provision of NAC were assessed following POD, before and after the implementation of an electronic prescribing tool.

Methods

The NAC electronic prescribing tool proposed the three NAC infusions (dosed for weight) following entry of the patient's weight. All NAC prescriptions were reviewed during a three-month period prior to and after the tool's implementation. Error rates were divided into dose, infusion volume or infusion rate. Delays in NAC provision were identified using national Emergency Medicine guidelines.

Results

108 NAC prescriptions were analysed for all adult patients admitted to the emergency department of a secondary care hospital in the UK between July-September 2017 and August-October 2018, respectively. There were no differences in the demographics of patients or the seniority of the prescribing clinician before or after the introduction of the electronic tool. The electronic prescribing tool was associated with a decrease in prescribing errors (25% to 0%, p < 0.0071) and an increase in the provision of NAC within recommended times (11.1% to 47.4%, p = 0.029).

Conclusions

An electronic prescribing tool improved prescription errors and the timeliness of NAC provision following POD. Further studies will determine the effect of this on length of stay and the benefit of wider implementation in other secondary care hospitals.",,doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render 34376451,https://doi.org/10.1136/bmjopen-2021-048852,Ethnic and social inequalities in COVID-19 outcomes in Scotland: protocol for early pandemic evaluation and enhanced surveillance of COVID-19 (EAVE II).,"Henery P, Vasileiou E, Hainey KJ, Buchanan D, Harrison E, Leyland AH, Alexis T, Robertson C, Agrawal U, Ritchie L, Stock SJ, McCowan C, Docherty A, Kerr S, Marple J, Wood R, Moore E, Simpson CR, Sheikh A, Katikireddi SV.",,BMJ open,2021,2021-08-10,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

Evidence from previous pandemics, and the current COVID-19 pandemic, has found that risk of infection/severity of disease is disproportionately higher for ethnic minority groups, and those in lower socioeconomic positions. It is imperative that interventions to prevent the spread of COVID-19 are targeted towards high-risk populations. We will investigate the associations between social characteristics (such as ethnicity, occupation and socioeconomic position) and COVID-19 outcomes and the extent to which characteristics/risk factors might explain observed relationships in Scotland.The primary objective of this study is to describe the epidemiology of COVID-19 by social factors. Secondary objectives are to (1) examine receipt of treatment and prevention of COVID-19 by social factors; (2) quantify ethnic/social differences in adverse COVID-19 outcomes; (3) explore potential mediators of relationships between social factors and SARS-CoV-2 infection/COVID-19 prognosis; (4) examine whether occupational COVID-19 differences differ by other social factors and (5) assess quality of ethnicity coding within National Health Service datasets.

Methods and analysis

We will use a national cohort comprising the adult population of Scotland who completed the 2011 Census and were living in Scotland on 31 March 2020 (~4.3 million people). Census data will be linked to the Early Assessment of Vaccine and Anti-Viral Effectiveness II cohort consisting of primary/secondary care, laboratory data and death records. Sensitivity/specificity and positive/negative predictive values will be used to assess coding quality of ethnicity. Descriptive statistics will be used to examine differences in treatment and prevention of COVID-19. Poisson/Cox regression analyses and mediation techniques will examine ethnic and social differences, and drivers of inequalities in COVID-19. Effect modification (on additive and multiplicative scales) between key variables (such as ethnicity and occupation) will be assessed.

Ethics and dissemination

Ethical approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers.",,doi:https://doi.org/10.1136/bmjopen-2021-048852; html:https://europepmc.org/articles/PMC8359861; pdf:https://europepmc.org/articles/PMC8359861?pdf=render +33240522,https://doi.org/10.1177/2055207620965046,Electronic-prescribing tools improve N-acetylcysteine prescription accuracy and timeliness for patients who present following a paracetamol overdose: A digital innovation quality-improvement project.,"McCulloch A, Sarwar A, Bate T, Thompson D, McDowell P, Sharif Q, Sapey E, Seccombe A.",,Digital health,2020,2020-01-01,Y,Antidote; Digital; paracetamol; Prescription Errors; Electronic Health Systems,,,"

Objectives

Prescription error rates and delays in treatment provision are high for N-acetylcysteine (NAC) when prescribed for paracetamol overdose (POD). We hypothesised that an electronic tool which proposed the complete NAC regimen would reduce prescription errors and improve the timeliness of NAC provision. Error rates and delays in the provision of NAC were assessed following POD, before and after the implementation of an electronic prescribing tool.

Methods

The NAC electronic prescribing tool proposed the three NAC infusions (dosed for weight) following entry of the patient's weight. All NAC prescriptions were reviewed during a three-month period prior to and after the tool's implementation. Error rates were divided into dose, infusion volume or infusion rate. Delays in NAC provision were identified using national Emergency Medicine guidelines.

Results

108 NAC prescriptions were analysed for all adult patients admitted to the emergency department of a secondary care hospital in the UK between July-September 2017 and August-October 2018, respectively. There were no differences in the demographics of patients or the seniority of the prescribing clinician before or after the introduction of the electronic tool. The electronic prescribing tool was associated with a decrease in prescribing errors (25% to 0%, p < 0.0071) and an increase in the provision of NAC within recommended times (11.1% to 47.4%, p = 0.029).

Conclusions

An electronic prescribing tool improved prescription errors and the timeliness of NAC provision following POD. Further studies will determine the effect of this on length of stay and the benefit of wider implementation in other secondary care hospitals.",,doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render 35902613,https://doi.org/10.1038/s41467-022-32096-4,Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England.,"Eales O, de Oliveira Martins L, Page AJ, Wang H, Bodinier B, Tang D, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly CA, Chadeau-Hyam M.",,Nature communications,2022,2022-07-28,Y,,,,"The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England's Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the 'new normal'.",,doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render 35726508,https://doi.org/10.1177/10398562221103117,Improving quantification of anticholinergic burden using the Anticholinergic Effect on Cognition Scale - a healthcare improvement study in a geriatric ward setting.,"Balasundaram B, Ang WST, Stewart R, Bishara D, Ooi CH, Li F, Akram F, Eu Kwek AB.",,Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists,2022,2022-06-21,Y,Dementia; Delirium; Anticholinergic drugs; Anticholinergic Burden Scales; Anticholinergic Effect On Cognition Scale,,,"

Objective

Anticholinergic burden refers to the cumulative effects of taking multiple medications with anticholinergic effects. This study was carried out in a public hospital in Singapore, aimed to improve and achieve a 100% comprehensive identification and review of measured, anticholinergic burden in a geriatric psychiatry liaison service to geriatric wards. We evaluated changes in pre-to post-assessment anticholinergic burden scores and trainee feedback.

Method

Plan Do Study Act methodology was employed, and Anticholinergic Effect on Cognition scale (AEC) was implemented as the study intervention. A survey instrument evaluated trainee feedback.

Results

There was no measured anticholinergic burden in a baseline of 170 assessments. 75 liaison psychiatry assessments were conducted between June and November 2021 in two cycles. 94.7% of pre-assessments (at the time of assessment) and 71.1% of post-assessments (following assessment) had a record of AEC scores in clinical documentation in cycle one, improving in the second cycle to 100%, 94.6%, respectively. A high post-assessment AEC score of 3 and over reduced from 15.8% in cycle one to 5.4% in cycle two. The trainee feedback suggested an enriching educational experience.

Conclusions

Using the AEC scale, the findings support the feasibility of comprehensive identification and review of measured anticholinergic burden in older people with neurocognitive disorders.",,doi:https://doi.org/10.1177/10398562221103117; html:https://europepmc.org/articles/PMC9379386; pdf:https://europepmc.org/articles/PMC9379386?pdf=render 33846368,https://doi.org/10.1038/s41598-021-86324-w,Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants.,"Laguzzi F, Maitusong B, Strawbridge RJ, Baldassarre D, Veglia F, Humphries SE, Rauramaa R, Kurl S, Smit AJ, Giral P, Silveira A, Tremoli E, Hamsten A, de Faire U, Gigante B, Leander K, IMPROVE Study group.",,Scientific reports,2021,2021-04-12,Y,,,,"The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54-79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point > zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06-1.47), CC-IMTmean (OR:1.22;1.04-1.44) and ICA-IMTmean (OR:1.26;1.07-1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis.",,doi:https://doi.org/10.1038/s41598-021-86324-w; html:https://europepmc.org/articles/PMC8042105; pdf:https://europepmc.org/articles/PMC8042105?pdf=render @@ -368,13 +369,13 @@ PMC10464864,https://doi.org/,Data linkage can reduce the burden and increase the 32499256,https://doi.org/10.1136/bmjopen-2019-033424,Point-of-care tests for urinary tract infections: protocol for a systematic review and meta-analysis of diagnostic test accuracy.,"Fraile Navarro D, Sullivan F, Azcoaga-Lorenzo A, Hernandez Santiago V.",,BMJ open,2020,2020-06-03,Y,Urinary tract infections; epidemiology; Molecular Diagnostics; Diagnostic Microbiology,,,"

Introduction

Urinary tract infections (UTIs) are the second most common type of infection worldwide, accounting for a large number of primary care consultations and antibiotic prescribing. Current diagnosis is based on an empirical approach, relying on symptoms and occasional use of urine dipsticks. The diagnostic reference standard is still urine culture, although it is not routinely recommended for uncomplicated UTIs in the community, due to time to diagnosis (48 hours). Faster point-of-care tests have been developed, but their diagnostic accuracy has not been compared. Our objective is to systematically review and meta-analyse the diagnostic accuracy of currently available point-of-care tests for UTIs.

Methods and analysis

Studies evaluating the diagnostic accuracy of point-of-care tests for UTIs will be included. PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews were searched from inception to 1 June 2019. Data extraction and risk-of-bias assessment will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta-analysis will be performed depending on data availability and heterogeneity.

Ethics and dissemination

This is a systematic review protocol and therefore formal ethical approval is not required, as no primary, identifiable, personal data will be collected. Patients or the public were not involved in the design of our research. However, the findings from this review will be shared with key stakeholders, including patient groups, clinicians and guideline developers, and will also be presented and national and international conferences.

Prospero registration number

CRD42018112019.",,doi:https://doi.org/10.1136/bmjopen-2019-033424; html:https://europepmc.org/articles/PMC7282288; pdf:https://europepmc.org/articles/PMC7282288?pdf=render 31757986,https://doi.org/10.1038/s41598-019-53454-1,Ontology-based prediction of cancer driver genes.,"Althubaiti S, Karwath A, Dallol A, Noor A, Alkhayyat SS, Alwassia R, Mineta K, Gojobori T, Beggs AD, Schofield PN, Gkoutos GV, Hoehndorf R.",,Scientific reports,2019,2019-11-22,Y,,Applied Analytics,,"Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.",This study investigated which genes encourage cancer tumors to grow. The study identifies genes and distinguishes their role in different types of cancers. Their method is validated using whole exome and whole genome sequencing,doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render; pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf 36735963,https://doi.org/10.1080/09553002.2023.2173823,Machine intelligence for radiation science: summary of the Radiation Research Society 67th annual meeting symposium.,"Wilson LJ, Kiffer FC, Berrios DC, Bryce-Atkinson A, Costes SV, Gevaert O, Matarèse BFE, Miller J, Mukherjee P, Peach K, Schofield PN, Slater LT, Langen B.",,International journal of radiation biology,2023,2023-02-06,N,Artificial intelligence; Lung cancer; Radiotherapy; Radiobiology; Ontology; Machine Learning; Voxel-based Analysis,,,"The era of high-throughput techniques created big data in the medical field and research disciplines. Machine intelligence (MI) approaches can overcome critical limitations on how those large-scale data sets are processed, analyzed, and interpreted. The 67th Annual Meeting of the Radiation Research Society featured a symposium on MI approaches to highlight recent advancements in the radiation sciences and their clinical applications. This article summarizes three of those presentations regarding recent developments for metadata processing and ontological formalization, data mining for radiation outcomes in pediatric oncology, and imaging in lung cancer.",,doi:https://doi.org/10.1080/09553002.2023.2173823 -36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render 33243817,https://doi.org/10.1136/bmjopen-2020-042813,COVID-19 in Pregnancy in Scotland (COPS): protocol for an observational study using linked Scottish national data.,"Stock SJ, McAllister D, Vasileiou E, Simpson CR, Stagg HR, Agrawal U, McCowan C, Hopkins L, Donaghy J, Ritchie L, Robertson C, Sheikh A, Wood R.",,BMJ open,2020,2020-11-26,Y,Obstetrics; epidemiology; Neonatology; Perinatology; Covid-19,,,"

Introduction

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

Methods and analysis

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

Ethics and dissemination

COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2020-042813; html:https://europepmc.org/articles/PMC7691999; pdf:https://europepmc.org/articles/PMC7691999?pdf=render 35379238,https://doi.org/10.1186/s12933-022-01482-z,Metformin and high-sensitivity cardiac troponin I and T trajectories in type 2 diabetes patients: a post-hoc analysis of a randomized controlled trial.,"Stultiens JMG, Top WMC, Kimenai DM, Lehert P, Bekers O, Stehouwer CDA, Kooy A, Meex SJR.",,Cardiovascular diabetology,2022,2022-04-04,Y,Troponin; Mechanism; Cardiac; Biomarker; Metformin; Longitudinal; Cardioprotective,,,"

Background

Metformin has favorable effects on cardiovascular outcomes in both newly onset and advanced type 2 diabetes, as previously reported findings from the UK Prospective Diabetes Study and the HOME trial have demonstrated. Patients with type 2 diabetes present with chronically elevated circulating cardiac troponin levels, an established predictor of cardiovascular endpoints and prognostic marker of subclinical myocardial injury. It is unknown whether metformin affects cardiac troponin levels. The study aimed to evaluate cardiac troponin I and T trajectories in patients with diabetes treated either with metformin or placebo.

Methods

This study is a post-hoc analysis of a randomized controlled trial (HOME trial) that included 390 patients with advanced type 2 diabetes randomized to 850 mg metformin or placebo up to three times daily concomitant to continued insulin treatment. Cardiac troponin I and T concentrations were measured at baseline and after 4, 17, 30, 43 and 52 months. We evaluated cardiac troponin trajectories by linear mixed-effects modeling, correcting for age, sex, smoking status and history of cardiovascular disease.

Results

This study enrolled 390 subjects, of which 196 received metformin and 194 received placebo. In the treatment and placebo groups, mean age was 64 and 59 years; with 50% and 58% of subjects of the female sex, respectively. Despite the previously reported reduction of macrovascular disease risk in this cohort by metformin, linear mixed-effects regression modelling did not reveal evidence for an effect on cardiac troponin I and cardiac troponin T levels [- 8.4% (- 18.6, 3.2), p = 0.150, and - 4.6% (- 12, 3.2), p = 0.242, respectively]. A statistically significant time-treatment interaction was found for troponin T [- 1.6% (- 2.9, - 0.2), p = 0.021] but not troponin I concentrations [- 1.5% (- 4.2, 1.2), p = 0.263].

Conclusions

In this post-hoc analysis of a 4.3-year randomized controlled trial, metformin did not exert a clinically relevant effect on cardiac troponin I and cardiac troponin T levels when compared to placebo. Cardioprotective effects of the drug observed in clinical studies are not reflected by a reduction in these biomarkers of subclinical myocardial injury. Trial registration ClinicalTrials.gov identifier NCT00375388.",,doi:https://doi.org/10.1186/s12933-022-01482-z; html:https://europepmc.org/articles/PMC8981770; pdf:https://europepmc.org/articles/PMC8981770?pdf=render +36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render 32935048,https://doi.org/10.23889/ijpds.v5i1.1121,The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC).,"Schnier C, Wilkinson T, Akbari A, Orton C, Sleegers K, Gallacher J, Lyons RA, Sudlow C.",,International journal of population data science,2020,2020-02-25,Y,,,,"

Introduction

The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care.

Objectives

We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers.

Methods

SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors.

Results

From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years.

Conclusion

We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.",,doi:https://doi.org/10.23889/ijpds.v5i1.1121; html:https://europepmc.org/articles/PMC7473277; pdf:https://europepmc.org/articles/PMC7473277?pdf=render 33004880,https://doi.org/10.1038/s41598-020-73228-4,"Predicting pattern formation in embryonic stem cells using a minimalist, agent-based probabilistic model.","Wang M, Tsanas A, Blin G, Robertson D.",,Scientific reports,2020,2020-10-01,Y,,,,"The mechanisms of pattern formation during embryonic development remain poorly understood. Embryonic stem cells in culture self-organise to form spatial patterns of gene expression upon geometrical confinement indicating that patterning is an emergent phenomenon that results from the many interactions between the cells. Here, we applied an agent-based modelling approach in order to identify plausible biological rules acting at the meso-scale within stem cell collectives that may explain spontaneous patterning. We tested different models involving differential motile behaviours with or without biases due to neighbour interactions. We introduced a new metric, termed stem cell aggregate pattern distance (SCAPD) to probabilistically assess the fitness of our models with empirical data. The best of our models improves fitness by 70% and 77% over the random models for a discoidal or an ellipsoidal stem cell confinement respectively. Collectively, our findings show that a parsimonious mechanism that involves differential motility is sufficient to explain the spontaneous patterning of the cells upon confinement. Our work also defines a region of the parameter space that is compatible with patterning. We hope that our approach will be applicable to many biological systems and will contribute towards facilitating progress by reducing the need for extensive and costly experiments.",,doi:https://doi.org/10.1038/s41598-020-73228-4; html:https://europepmc.org/articles/PMC7529768; pdf:https://europepmc.org/articles/PMC7529768?pdf=render -37236697,https://doi.org/10.1016/s2589-7500(23)00065-1,"Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study.","Banerjee A, Dashtban A, Chen S, Pasea L, Thygesen JH, Fatemifar G, Tyl B, Dyszynski T, Asselbergs FW, Lund LH, Lumbers T, Denaxas S, Hemingway H.",,The Lancet. Digital health,2023,2023-06-01,N,,,,"

Background

Machine learning has been used to analyse heart failure subtypes, but not across large, distinct, population-based datasets, across the whole spectrum of causes and presentations, or with clinical and non-clinical validation by different machine learning methods. Using our published framework, we aimed to discover heart failure subtypes and validate them upon population representative data.

Methods

In this external, prognostic, and genetic validation study we analysed individuals aged 30 years or older with incident heart failure from two population-based databases in the UK (Clinical Practice Research Datalink [CPRD] and The Health Improvement Network [THIN]) from 1998 to 2018. Pre-heart failure and post-heart failure factors (n=645) included demographic information, history, examination, blood laboratory values, and medications. We identified subtypes using four unsupervised machine learning methods (K-means, hierarchical, K-Medoids, and mixture model clustering) with 87 of 645 factors in each dataset. We evaluated subtypes for (1) external validity (across datasets); (2) prognostic validity (predictive accuracy for 1-year mortality); and (3) genetic validity (UK Biobank), association with polygenic risk score (PRS) for heart failure-related traits (n=11), and single nucleotide polymorphisms (n=12).

Findings

We included 188 800, 124 262, and 9573 individuals with incident heart failure from CPRD, THIN, and UK Biobank, respectively, between Jan 1, 1998, and Jan 1, 2018. After identifying five clusters, we labelled heart failure subtypes as (1) early onset, (2) late onset, (3) atrial fibrillation related, (4) metabolic, and (5) cardiometabolic. In the external validity analysis, subtypes were similar across datasets (c-statistics: THIN model in CPRD ranged from 0·79 [subtype 3] to 0·94 [subtype 1], and CPRD model in THIN ranged from 0·79 [subtype 1] to 0·92 [subtypes 2 and 5]). In the prognostic validity analysis, 1-year all-cause mortality after heart failure diagnosis (subtype 1 0·20 [95% CI 0·14-0·25], subtype 2 0·46 [0·43-0·49], subtype 3 0·61 [0·57-0·64], subtype 4 0·11 [0·07-0·16], and subtype 5 0·37 [0·32-0·41]) differed across subtypes in CPRD and THIN data, as did risk of non-fatal cardiovascular diseases and all-cause hospitalisation. In the genetic validity analysis the atrial fibrillation-related subtype showed associations with the related PRS. Late onset and cardiometabolic subtypes were the most similar and strongly associated with PRS for hypertension, myocardial infarction, and obesity (p<0·0009). We developed a prototype app for routine clinical use, which could enable evaluation of effectiveness and cost-effectiveness.

Interpretation

Across four methods and three datasets, including genetic data, in the largest study of incident heart failure to date, we identified five machine learning-informed subtypes, which might inform aetiological research, clinical risk prediction, and the design of heart failure trials.

Funding

European Union Innovative Medicines Initiative-2.",,doi:https://doi.org/10.1016/S2589-7500(23)00065-1 33611594,https://doi.org/10.1093/eurjpc/zwaa155,Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.,"Banerjee A, Chen S, Pasea L, Lai AG, Katsoulis M, Denaxas S, Nafilyan V, Williams B, Wong WK, Bakhai A, Khunti K, Pillay D, Noursadeghi M, Wu H, Pareek N, Bromage D, McDonagh TA, Byrne J, Teo JTH, Shah AM, Humberstone B, Tang LV, Shah ASV, Rubboli A, Guo Y, Hu Y, Sudlow CLM, Lip GYH, Hemingway H.",,European journal of preventive cardiology,2021,2021-12-01,Y,Cardiovascular disease; Public Health; Health Policy; Global Health; Coronavirus-2019,,,"

Aims

Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.

Methods and results

We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.

Conclusion

Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.",,doi:https://doi.org/10.1093/eurjpc/zwaa155; html:https://europepmc.org/articles/PMC7928969; pdf:https://europepmc.org/articles/PMC7928969?pdf=render; pdf:https://academic.oup.com/eurjpc/article-pdf/28/14/1599/41827245/zwaa155.pdf +37236697,https://doi.org/10.1016/s2589-7500(23)00065-1,"Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study.","Banerjee A, Dashtban A, Chen S, Pasea L, Thygesen JH, Fatemifar G, Tyl B, Dyszynski T, Asselbergs FW, Lund LH, Lumbers T, Denaxas S, Hemingway H.",,The Lancet. Digital health,2023,2023-06-01,N,,,,"

Background

Machine learning has been used to analyse heart failure subtypes, but not across large, distinct, population-based datasets, across the whole spectrum of causes and presentations, or with clinical and non-clinical validation by different machine learning methods. Using our published framework, we aimed to discover heart failure subtypes and validate them upon population representative data.

Methods

In this external, prognostic, and genetic validation study we analysed individuals aged 30 years or older with incident heart failure from two population-based databases in the UK (Clinical Practice Research Datalink [CPRD] and The Health Improvement Network [THIN]) from 1998 to 2018. Pre-heart failure and post-heart failure factors (n=645) included demographic information, history, examination, blood laboratory values, and medications. We identified subtypes using four unsupervised machine learning methods (K-means, hierarchical, K-Medoids, and mixture model clustering) with 87 of 645 factors in each dataset. We evaluated subtypes for (1) external validity (across datasets); (2) prognostic validity (predictive accuracy for 1-year mortality); and (3) genetic validity (UK Biobank), association with polygenic risk score (PRS) for heart failure-related traits (n=11), and single nucleotide polymorphisms (n=12).

Findings

We included 188 800, 124 262, and 9573 individuals with incident heart failure from CPRD, THIN, and UK Biobank, respectively, between Jan 1, 1998, and Jan 1, 2018. After identifying five clusters, we labelled heart failure subtypes as (1) early onset, (2) late onset, (3) atrial fibrillation related, (4) metabolic, and (5) cardiometabolic. In the external validity analysis, subtypes were similar across datasets (c-statistics: THIN model in CPRD ranged from 0·79 [subtype 3] to 0·94 [subtype 1], and CPRD model in THIN ranged from 0·79 [subtype 1] to 0·92 [subtypes 2 and 5]). In the prognostic validity analysis, 1-year all-cause mortality after heart failure diagnosis (subtype 1 0·20 [95% CI 0·14-0·25], subtype 2 0·46 [0·43-0·49], subtype 3 0·61 [0·57-0·64], subtype 4 0·11 [0·07-0·16], and subtype 5 0·37 [0·32-0·41]) differed across subtypes in CPRD and THIN data, as did risk of non-fatal cardiovascular diseases and all-cause hospitalisation. In the genetic validity analysis the atrial fibrillation-related subtype showed associations with the related PRS. Late onset and cardiometabolic subtypes were the most similar and strongly associated with PRS for hypertension, myocardial infarction, and obesity (p<0·0009). We developed a prototype app for routine clinical use, which could enable evaluation of effectiveness and cost-effectiveness.

Interpretation

Across four methods and three datasets, including genetic data, in the largest study of incident heart failure to date, we identified five machine learning-informed subtypes, which might inform aetiological research, clinical risk prediction, and the design of heart failure trials.

Funding

European Union Innovative Medicines Initiative-2.",,doi:https://doi.org/10.1016/S2589-7500(23)00065-1 34599527,https://doi.org/10.1111/dme.14707,Comparing survival outcomes for kidney transplant recipients with pre-existing diabetes versus those who develop post-transplantation diabetes.,"Hussain A, Culliford A, Phagura N, Evison F, Gallier S, Sharif A.",,Diabetic medicine : a journal of the British Diabetic Association,2022,2021-10-08,N,Survival; Management; Diabetes; Kidney Transplant; Post-transplant Diabetes,,,"

Introduction

The aim of this study was to compare the management strategy and clinical outcomes for kidney transplant recipients with pre-transplant versus post-transplantation diabetes (PTDM) in a contemporary cohort.

Methods

This is a single-centre, retrospective. observational study of kidney transplant recipients between 2007 and 2018 with follow-up to 31 December 2020. Data were extracted from hospital electronic patient records, with clinical outcomes linked to national data sets. PTDM was diagnosed by international consensus guidelines. Unadjusted and adjusted survival outcomes were assessed with Kaplan-Meier curves and Cox regression models, respectively, with PTDM handled as a time-varying covariate.

Results

Data were analysed for 1,757 kidney transplant recipients, of whom 11.8% (n = 207) had pre-transplant diabetes, and 13.8% (n = 243) developed PTDM with median time to onset 108 days (IQR 46-549 days). Median follow-up was 1,839 days (IQR 928-2985 days). Disparate management strategies were observed, although insulin was the commonest glucose-lowering therapy for all patients with diabetes. In adjusted models, PTDM was associated with lower mortality (HR 0.663, 95% CI 0.543-0.810) and pre-diabetes with higher mortality (HR 1.675, 95% CI 1.396-2.011). However, if analyses are restricted to those with at least 5-year follow-up, then PTDM has no association with mortality (HR 0.771, 95% CI 0.419-1.096), but pre-transplant diabetes remains associated with higher mortality (HR 2.029, 95% CI 1.367-3.012).

Conclusions

Pre-transplant diabetes remains associated with increased mortality risk after kidney transplantation, but PTDM effects are time dependent. Development of PTDM should be encouraged as a mandated registry return to study the long-term impact on survival outcomes.",,doi:https://doi.org/10.1111/dme.14707 36745545,https://doi.org/10.1099/mgen.0.000887,The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021.,"Eales O, Page AJ, Tang SN, Walters CE, Wang H, Haw D, Trotter AJ, Le Viet T, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly CA, O'Grady J, Volz E, The Covid-Genomics Uk Cog-Uk Consortium, Darzi A, Ward H, Elliott P, Riley S.",,Microbial genomics,2023,2023-02-01,Y,,,,"Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity.",,doi:https://doi.org/10.1099/mgen.0.000887; html:https://europepmc.org/articles/PMC9997751; pdf:https://europepmc.org/articles/PMC9997751?pdf=render 34966903,https://doi.org/10.3389/fdgth.2021.778305,Development of a Lexicon for Pain.,"Chaturvedi J, Mascio A, Velupillai SU, Roberts A.",,Frontiers in digital health,2021,2021-12-13,Y,Pain; Mental health; Lexicon; Electronic Health Records; Natural Language Processing,,,"Pain has been an area of growing interest in the past decade and is known to be associated with mental health issues. Due to the ambiguous nature of how pain is described in text, it presents a unique natural language processing (NLP) challenge. Understanding how pain is described in text and utilizing this knowledge to improve NLP tasks would be of substantial clinical importance. Not much work has previously been done in this space. For this reason, and in order to develop an English lexicon for use in NLP applications, an exploration of pain concepts within free text was conducted. The exploratory text sources included two hospital databases, a social media platform (Twitter), and an online community (Reddit). This exploration helped select appropriate sources and inform the construction of a pain lexicon. The terms within the final lexicon were derived from three sources-literature, ontologies, and word embedding models. This lexicon was validated by two clinicians as well as compared to an existing 26-term pain sub-ontology and MeSH (Medical Subject Headings) terms. The final validated lexicon consists of 382 terms and will be used in downstream NLP tasks by helping select appropriate pain-related documents from electronic health record (EHR) databases, as well as pre-annotating these words to help in development of an NLP application for classification of mentions of pain within the documents. The lexicon and the code used to generate the embedding models have been made publicly available.",,doi:https://doi.org/10.3389/fdgth.2021.778305; html:https://europepmc.org/articles/PMC8710455; pdf:https://europepmc.org/articles/PMC8710455?pdf=render @@ -392,9 +393,9 @@ PMC10464864,https://doi.org/,Data linkage can reduce the burden and increase the 34261639,https://doi.org/10.1136/bmj.n1592,Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform.,"Williamson EJ, McDonald HI, Bhaskaran K, Walker AJ, Bacon S, Davy S, Schultze A, Tomlinson L, Bates C, Ramsay M, Curtis HJ, Forbes H, Wing K, Minassian C, Tazare J, Morton CE, Nightingale E, Mehrkar A, Evans D, Inglesby P, MacKenna B, Cockburn J, Rentsch CT, Mathur R, Wong AYS, Eggo RM, Hulme W, Croker R, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Smeeth L, Goldacre B, Kuper H.",,BMJ (Clinical research ed.),2021,2021-07-14,Y,,,,"

Objective

To assess the association between learning disability and risk of hospital admission and death from covid-19 in England among adults and children.

Design

Population based cohort study on behalf of NHS England using the OpenSAFELY platform.

Setting

Patient level data were obtained for more than 17 million people registered with a general practice in England that uses TPP software. Electronic health records were linked with death data from the Office for National Statistics and hospital admission data from NHS Secondary Uses Service.

Participants

Adults (aged 16-105 years) and children (<16 years) from two cohorts: wave 1 (registered with a TPP practice as of 1 March 2020 and followed until 31 August 2020); and wave 2 (registered 1 September 2020 and followed until 8 February 2021). The main exposure group consisted of people on a general practice learning disability register; a subgroup was defined as those having profound or severe learning disability. People with Down's syndrome and cerebral palsy were identified (whether or not they were on the learning disability register).

Main outcome measure

Covid-19 related hospital admission and covid-19 related death. Non-covid-19 deaths were also explored.

Results

For wave 1, 14 312 023 adults aged ≥16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a covid-19 related hospital admission; there were 222 (0.25%) covid-19 related deaths and 602 (0.7%) non-covid deaths. Among adults not on the register, 29 781 (0.2%) had a covid-19 related hospital admission; there were 13 737 (0.1%) covid-19 related deaths and 69 837 (0.5%) non-covid deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for covid-19 related hospital admission and 8.2 (7.2 to 9.4) for covid-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down's syndrome and cerebral palsy were associated with increased hazards for both events; Down's syndrome to a greater extent. Hazard ratios for non-covid deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but covid-19 related deaths and hospital admissions were rare, reflecting low event rates among children.

Conclusions

People with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Prompt access to covid-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for covid-19 vaccination and other targeted preventive measures should be considered.",,doi:https://doi.org/10.1136/bmj.n1592; html:https://europepmc.org/articles/PMC8278652; pdf:https://europepmc.org/articles/PMC8278652?pdf=render 34282121,https://doi.org/10.1038/s41398-021-01522-4,Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank.,"Zhu X, Ward J, Cullen B, Lyall DM, Strawbridge RJ, Lyall LM, Smith DJ.",,Translational psychiatry,2021,2021-07-16,Y,,,,"Anhedonia is a core symptom of multiple psychiatric disorders and has been associated with alterations in brain structure. Genome-wide association studies suggest that anhedonia is heritable, with a polygenic architecture, but few studies have explored the association between genetic loading for anhedonia-indexed by polygenic risk scores for anhedonia (PRS-anhedonia)-and structural brain imaging phenotypes. Here, we investigated how anhedonia and PRS-anhedonia were associated with brain structure within the UK Biobank cohort. Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness (CT) and white matter integrity) were analysed using linear mixed models in relation to anhedonia and PRS-anhedonia in 19,592 participants (9225 males; mean age = 62.6 years, SD = 7.44). We found that state anhedonia was significantly associated with reduced total grey matter volume (GMV); increased total white matter volume (WMV); smaller volumes in thalamus and nucleus accumbens; reduced CT within the paracentral cortex, the opercular part of inferior frontal gyrus, precentral cortex, insula and rostral anterior cingulate cortex; and poorer integrity of many white matter tracts. PRS-anhedonia was associated with reduced total GMV; increased total WMV; reduced white matter integrity; and reduced CT within the parahippocampal cortex, superior temporal gyrus and insula. Overall, both state anhedonia and PRS-anhedonia were associated with individual differences in multiple brain structures, including within reward-related circuits. These associations may represent vulnerability markers for psychopathology relevant to a range of psychiatric disorders.",,doi:https://doi.org/10.1038/s41398-021-01522-4; html:https://europepmc.org/articles/PMC8289859; pdf:https://europepmc.org/articles/PMC8289859?pdf=render 35213664,https://doi.org/10.1371/journal.pone.0264529,Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.,"Ellins EA, Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, John A, Gravenor MB, Halcox JP.",,PloS one,2022,2022-02-25,Y,,,,"

Aims

To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients.

Methods & findings

A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data.

Conclusion

Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.",,doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render +35474585,https://doi.org/10.1111/bcp.15366,Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.,"Subramanian A, Han D, Braithwaite T, Thayakaran R, Zemedikun DT, Gokhale KM, Lee WH, Coker J, Keane PA, Denniston AK, Nirantharakumar K, Azoulay L, Adderley NJ.",,British journal of clinical pharmacology,2022,2022-05-11,Y,Hypertension; Angiotensin-converting enzyme inhibitors; Age-related macular degeneration,,,"

Aims

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.

Methods

In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.

Results

During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively).

Conclusion

We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.",,doi:https://doi.org/10.1111/bcp.15366; html:https://europepmc.org/articles/PMC9541840; pdf:https://europepmc.org/articles/PMC9541840?pdf=render 34782484,https://doi.org/10.1136/thoraxjnl-2021-217580,External validation of the QCovid risk prediction algorithm for risk of COVID-19 hospitalisation and mortality in adults: national validation cohort study in Scotland.,"Simpson CR, Robertson C, Kerr S, Shi T, Vasileiou E, Moore E, McCowan C, Agrawal U, Docherty A, Mulholland R, Murray J, Ritchie LD, McMenamin J, Hippisley-Cox J, Sheikh A.",,Thorax,2022,2021-11-15,Y,Clinical Epidemiology; Covid-19,,,"

Background

The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland.

Methods

We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020.

Results

Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell's C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell's C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively.

Conclusions

Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively.",,doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?pdf=render 32576605,https://doi.org/10.1136/jech-2020-214051,Efficacy of contact tracing for the containment of the 2019 novel coronavirus (COVID-19).,"Keeling MJ, Hollingsworth TD, Read JM.",,Journal of epidemiology and community health,2020,2020-06-23,Y,epidemiology; Communicable Diseases; Public Health Policy; Disease Modeling,,,"

Objective

Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel coronavirus (COVID-19) from China and elsewhere into the UK highlights the need to understand the impact of contact tracing as a control measure.

Design

Detailed survey information on social encounters from over 5800 respondents is coupled to predictive models of contact tracing and control. This is used to investigate the likely efficacy of contact tracing and the distribution of secondary cases that may go untraced.

Results

Taking recent estimates for COVID-19 transmission we predict that under effective contact tracing less than 1 in 6 cases will generate any subsequent untraced infections, although this comes at a high logistical burden with an average of 36 individuals traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we find that tracing using a contact definition requiring more than 4 hours of contact is unlikely to control spread.

Conclusions

The current contact tracing strategy within the UK is likely to identify a sufficient proportion of infected individuals such that subsequent spread could be prevented, although the ultimate success will depend on the rapid detection of cases and isolation of contacts. Given the burden of tracing a large number of contacts to find new cases, there is the potential the system could be overwhelmed if imports of infection occur at a rapid rate.",,doi:https://doi.org/10.1136/jech-2020-214051; html:https://europepmc.org/articles/PMC7307459; pdf:https://europepmc.org/articles/PMC7307459?pdf=render; pdf:https://jech.bmj.com/content/jech/74/10/861.full.pdf -35474585,https://doi.org/10.1111/bcp.15366,Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.,"Subramanian A, Han D, Braithwaite T, Thayakaran R, Zemedikun DT, Gokhale KM, Lee WH, Coker J, Keane PA, Denniston AK, Nirantharakumar K, Azoulay L, Adderley NJ.",,British journal of clinical pharmacology,2022,2022-05-11,Y,Hypertension; Angiotensin-converting enzyme inhibitors; Age-related macular degeneration,,,"

Aims

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.

Methods

In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.

Results

During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively).

Conclusion

We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.",,doi:https://doi.org/10.1111/bcp.15366; html:https://europepmc.org/articles/PMC9541840; pdf:https://europepmc.org/articles/PMC9541840?pdf=render 33114263,https://doi.org/10.3390/ijms21217886,Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference. ,"Aziz F, Acharjee A, Williams JA, Russ D, Bravo-Merodio L, Gkoutos GV.",,International journal of molecular sciences,2020,2020-10-23,Y,,,,"Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the UGT1A family genes were identified as key regulators while upon analysing the PDAC dataset, the SULF1 and THBS2 genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.",,doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render 34356905,https://doi.org/10.3390/biomedicines9070841,Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study. ,"Coggi D, Frigerio B, Bonomi A, Ruscica M, Ferri N, Sansaro D, Ravani A, Ferrante P, Damigella M, Veglia F, Capra N, Lupo MG, Macchi C, Savonen K, Silveira A, Kurl S, Giral P, Pirro M, Strawbridge RJ, Gigante B, Smit AJ, Tremoli E, Amato M, Baldassarre D, On Behalf Of The Improve Study Group.",,Biomedicines,2021,2021-07-19,Y,,,,"(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54-79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.",,doi:https://doi.org/10.3390/biomedicines9070841; html:https://europepmc.org/articles/PMC8301759; pdf:https://europepmc.org/articles/PMC8301759?pdf=render 34957254,https://doi.org/10.3389/fcvm.2021.766287,Radiomics Analysis Derived From LGE-MRI Predict Sudden Cardiac Death in Participants With Hypertrophic Cardiomyopathy.,"Wang J, Bravo L, Zhang J, Liu W, Wan K, Sun J, Zhu Y, Han Y, Gkoutos GV, Chen Y.",,Frontiers in cardiovascular medicine,2021,2021-12-10,Y,hypertrophic cardiomyopathy; Sudden Cardiac Death; Machine Learning; Late Gadolinium Enhancement; Radiomics,,,"Objectives: To identify significant radiomics features derived from late gadolinium enhancement (LGE) images in participants with hypertrophic cardiomyopathy (HCM) and assess their prognostic value in predicting sudden cardiac death (SCD) endpoint. Method: The 157 radiomic features of 379 sequential participants with HCM who underwent cardiovascular magnetic resonance imaging (MRI) were extracted. CoxNet (Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net) and Random Forest models were applied to optimize feature selection for the SCD risk prediction and cross-validation was performed. Results: During a median follow-up of 29 months (interquartile range, 20-42 months), 27 participants with HCM experienced SCD events. Cox analysis revealed that two selected features, local binary patterns (LBP) (19) (hazard ratio (HR), 1.028, 95% CI: 1.032-1.134; P = 0.001) and Moment (1) (HR, 1.212, 95%CI: 1.032-1.423; P = 0.02) provided significant prognostic value to predict the SCD endpoints after adjustment for the clinical risk predictors and late gadolinium enhancement. Furthermore, the univariately significant risk predictor was improved by the addition of the selected radiomics features, LBP (19) and Moment (1), to predict SCD events (P < 0.05). Conclusion: The radiomics features of LBP (19) and Moment (1) extracted from LGE images, reflecting scar heterogeneity, have independent prognostic value in identifying high SCD risk patients with HCM.",,doi:https://doi.org/10.3389/fcvm.2021.766287; html:https://europepmc.org/articles/PMC8702805; pdf:https://europepmc.org/articles/PMC8702805?pdf=render @@ -412,14 +413,14 @@ PMC10464864,https://doi.org/,Data linkage can reduce the burden and increase the 36543718,https://doi.org/10.1016/j.ebiom.2022.104402,SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.,"Liew F, Talwar S, Cross A, Willett BJ, Scott S, Logan N, Siggins MK, Swieboda D, Sidhu JK, Efstathiou C, Moore SC, Davis C, Mohamed N, Nunag J, King C, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton DG, Dunachie S, Quint JK, Evans RA, Wain LV, Fontanella S, de Silva TI, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites RS, Turtle L, Openshaw PJM, ISARIC4C Investigators, PHOSP-COVID collaborative group.",,EBioMedicine,2023,2022-12-19,Y,Vaccination; Mucosal immunity; Convalescent; Covid-19; Sars-cov-2 Immunity; Sars-cov-2 Variants; Nasal Antibody,,,"

Background

Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods

In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.

Findings

Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.

Interpretation

The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

Funding

This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.",,doi:https://doi.org/10.1016/j.ebiom.2022.104402; html:https://europepmc.org/articles/PMC9762734; pdf:https://europepmc.org/articles/PMC9762734?pdf=render; doi:https://doi.org/10.1016/j.ebiom.2022.104402 35677101,https://doi.org/10.23889/ijpds.v5i4.1715,"Impact of COVID-19 pandemic on community medication dispensing: a national cohort analysis in Wales, UK.","Torabi F, Akbari A, Bedston S, Davies G, Abbasizanjani H, Gravenor M, Griffiths R, Harris D, Jenkins N, Lyons J, Morris A, North L, Halcox J, Lyons RA.",,International journal of population data science,2020,2020-01-01,Y,Public Health; Covid-19; Dispensed Medication; Community Dispensing; Interactive Dispensing Dashboard,,,"

Background

Population-level information on dispensed medication provides insight on the distribution of treated morbidities, particularly if linked to other population-scale data at an individual-level.

Objective

To evaluate the impact of COVID-19 on dispensing patterns of medications.

Methods

Retrospective observational study using population-scale, individual-level dispensing records in Wales, UK. Total dispensed drug items for the population between 1 st January 2016 and 31 st December 2019 (3-years, pre-COVID-19) were compared to 2020 with follow up until 27 th July 2021 (COVID-19 period). We compared trends across all years and British National Formulary (BNF) chapters and highlighted the trends in three major chapters for 2019-21: 1-Cardiovascular system (CVD); 2-Central Nervous System (CNS); 3-Immunological & Vaccine. We developed an interactive dashboard to enable monitoring of changes as the pandemic evolves.

Result

Amongst all BNF chapters, 73,410,543 items were dispensed in 2020 compared to 74,121,180 items in 2019 demonstrating -0.96% relative decrease in 2020. Comparison of monthly patterns showed average difference (D) of -59,220 and average Relative Change (RC) of -0.74% between the number of dispensed items in 2020 and 2019. Maximum RC was observed in March 2020 (D = +1,224,909 and RC = +20.62), followed by second peak in June 2020 (D = +257,920, RC = +4.50%). A third peak was observed in September 2020 (D = +264,138, RC = +4.35%). Large increases in March 2020 were observed for CVD and CNS medications across all age groups. The Immunological and Vaccine products dropped to very low levels across all age groups and all months (including the March dispensing peak).

Conclusions

Reconfiguration of routine clinical services during COVID-19 led to substantial changes in community pharmacy drug dispensing. This change may contribute to a long-term burden of COVID-19, raising the importance of a comprehensive and timely monitoring of changes for evaluation of the potential impact on clinical care and outcomes.",,doi:https://doi.org/10.23889/ijpds.v5i4.1715; html:https://europepmc.org/articles/PMC9135049; pdf:https://europepmc.org/articles/PMC9135049?pdf=render PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in Wales.,"Fry R, Hollinghurst J, North L, Emmerson C, Long S, Akbari A, Gravenor M, Lyons R.",,International journal of population data science,,2022-11-21,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644982; pdf:https://europepmc.org/articles/PMC9644982?pdf=render -34644365,https://doi.org/10.1371/journal.pone.0258484,Cohort profile: The UK COVID-19 Public Experiences (COPE) prospective longitudinal mixed-methods study of health and well-being during the SARSCoV2 coronavirus pandemic.,"Phillips R, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Peddle S, Campbell S, Hughes K, Gillespie D, Sellars P, Pell B, Ashfield-Watt P, Akbari A, Seage CH, Perham N, Joseph-Williams N, Harrop E, Blaxland J, Wood F, Poortinga W, Wahl-Jorgensen K, James DH, Crone D, Thomas-Jones E, Hallingberg B.",,PloS one,2021,2021-10-13,Y,,,,"Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.",,doi:https://doi.org/10.1371/journal.pone.0258484; html:https://europepmc.org/articles/PMC8513913; pdf:https://europepmc.org/articles/PMC8513913?pdf=render 34632260,https://doi.org/10.1093/rap/rkab042,"Biologic use in psoriatic arthritis and ankylosing spondylitis patients: a descriptive epidemiological study using linked, routine data in Wales, UK.","Cooksey R, Rahman MA, Kennedy J, Brophy S, Choy E.",,Rheumatology advances in practice,2021,2021-06-27,Y,Ankylosing spondylitis; Psoriatic Arthritis; Outcomes; Biologics; Electronic Health Records; Treatment Pathways,,,"

Objectives

PsA and AS are chronic diseases associated with significant morbidities. National and international management guidelines include treatment with biologic therapies to improve outcomes and quality of life. There are limited real-world data on the patients' journey from symptom onset to diagnosis and treatment in the UK. We use real-life, linked health data to explore patient pathways and the impact of biologics on patient outcomes.

Methods

Data from the Secure Anonymised Information Linkage databank in Wales were used to assess diagnosis and treatment of patients ≥18 years of age with at least one International Classification of Diseases, Tenth Revision code present for PsA/AS in rheumatology clinic data and at least one Read code present in primary care records. We investigated the use of biologics while exploring demographics, comorbidities and surgical procedures of 641 AS patients and 1312 PsA patients.

Results

AS patients were significantly younger at diagnosis and were predominantly male. The average time from presenting symptoms to diagnosis of AS and PsA was 7.9 (s.d. 5.5) and 9.3 (s.d. 5.5) years, respectively. The proportion of patients receiving biologic treatment was significantly higher in AS (46%) compared with PsA patients (28.8%); of these, 23.1% of AS and 22.2% of PsA patients stopped/switched a biologic. There was a significant reduction in primary care involvement, sick notes and disability living allowance for both AS and PsA patients following biologic initiation.

Conclusion

This real-world descriptive study confirms that patients treated with biologics have reduced disability and time off work despite being initiated ∼13 years after the first symptoms and 6 years after diagnosis.",,doi:https://doi.org/10.1093/rap/rkab042; html:https://europepmc.org/articles/PMC8496109; pdf:https://europepmc.org/articles/PMC8496109?pdf=render +34644365,https://doi.org/10.1371/journal.pone.0258484,Cohort profile: The UK COVID-19 Public Experiences (COPE) prospective longitudinal mixed-methods study of health and well-being during the SARSCoV2 coronavirus pandemic.,"Phillips R, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Peddle S, Campbell S, Hughes K, Gillespie D, Sellars P, Pell B, Ashfield-Watt P, Akbari A, Seage CH, Perham N, Joseph-Williams N, Harrop E, Blaxland J, Wood F, Poortinga W, Wahl-Jorgensen K, James DH, Crone D, Thomas-Jones E, Hallingberg B.",,PloS one,2021,2021-10-13,Y,,,,"Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.",,doi:https://doi.org/10.1371/journal.pone.0258484; html:https://europepmc.org/articles/PMC8513913; pdf:https://europepmc.org/articles/PMC8513913?pdf=render 36992264,https://doi.org/10.3390/vaccines11030680,"Determinants of Equity in Coverage of Measles-Containing Vaccines in Wales, UK, during the Elimination Era.","Perry M, Cottrell S, Gravenor MB, Griffiths L.",,Vaccines,2023,2023-03-17,Y,"Vaccination; Measles; Socioeconomic Factors; Immunisation; Mmr; Measles, Mumps And Rubella Vaccine",,,"In the context of the WHO's measles and rubella elimination targets and European Immunization Agenda 2030, this large cross-sectional study aimed to identify inequalities in measles vaccination coverage in Wales, UK. The vaccination status of individuals aged 2 to 25 years of age, alive and resident in Wales as of 31 August 2021, was ascertained through linkage of the National Community Child Health Database and primary care data. A series of predictor variables were derived from five national datasets and all analysis was carried out in the Secure Anonymised Information Linkage Databank at Swansea University. In these 648,895 individuals, coverage of the first dose of measles-containing vaccine (due at 12-13 months of age) was 97.1%, and coverage of the second dose (due at 3 years and 4 months) in 4 to 25-year-olds was 93.8%. In multivariable analysis, excluding 0.7% with known refusal, the strongest association with being unvaccinated was birth order (families with six or more children) and being born outside of the UK. Living in a deprived area, being eligible for free school meals, a lower level of maternal education, and having a recorded language other than English or Welsh were also associated with lower coverage. Some of these factors may also be associated with refusal. This knowledge can be used to target future interventions and prioritise areas for catch up in a time of limited resource.",,doi:https://doi.org/10.3390/vaccines11030680; html:https://europepmc.org/articles/PMC10057771; pdf:https://europepmc.org/articles/PMC10057771?pdf=render 36036238,https://doi.org/10.1002/clt2.12180,Mixed-methods evaluation of a nurse-led allergy clinic model in primary care: Feasibility trial.,"Hammersley V, Kelman M, Morrice L, Kendall M, Mukerjhee M, Harley S, Schwarze J, Sheikh A.",,Clinical and translational allergy,2022,2022-08-01,Y,Allergy; Quality of life; Primary Care,,,"

Introduction

It is now widely acknowledged that there are serious shortcomings in allergy care provision for patients seen in primary care. We sought to assess the feasibility of delivering and evaluating a new nurse-led allergy service in primary care, measured by recruitment, retention and estimates of the potential impact of the intervention on disease-specific quality of life.

Methods

Mixed-methods evaluation of a nurse-led primary care-based allergy clinic in Edinburgh, UK undertaken during the period 2017-2021 with a focus on suspected food allergy and atopic eczema in young children, allergic rhinitis in children and young people, and suspected anaphylaxis in adults. Prior to March 2020, patients were seen face-to-face (Phase 1). Due to COVID-19 pandemic restrictions, recruitment was halted between March-August 2020, and a remote clinic was restarted in September 2020 (Phase 2). Disease-specific quality of life was measured at baseline and 6-12 weeks post intervention using validated instruments. Quantitative data were descriptively analysed. We undertook interviews with 16 carers/patients and nine healthcare professionals, which were thematically analysed.

Results

During Phase 1, 426/506 (84%) referred patients met the eligibility criteria; 40/46 (87%) of Phase 2 referrals were eligible. Males and females were recruited in approximately equal numbers. The majority (83%) of referrals were for possible food allergy or anaphylaxis. Complete data were available for 338/426 (79%) patients seen in Phase 1 and 30/40 (75%) in Phase 2. Compared with baseline assessments, there were improvements in disease-specific quality of life for most categories of patients. Patients/carers and healthcare professionals reported high levels of satisfaction, this being reinforced by the qualitative interviews in which convenience and speed of access to expert opinion, the quality of the consultation, and patient/care empowerment were particularly emphasised.

Conclusion

This large feasibility trial has demonstrated that it is possible to recruit, deliver and retain individuals into a nurse-led allergy clinic with both face-to-face and remote consultations. Our data indicate that the intervention was considered acceptable to patients/carers and healthcare professionals. The before-after data of disease-specific quality of life suggest that the intervention may prove effective, but this now needs to be confirmed through a formal randomised controlled trial.

Trial registration

ClinicalTrials.gov reference NCT03826953.",,doi:https://doi.org/10.1002/clt2.12180; html:https://europepmc.org/articles/PMC9362986; pdf:https://europepmc.org/articles/PMC9362986?pdf=render 31658860,https://doi.org/10.1161/jaha.119.012812,Early Discontinuation of P2Y12 Antagonists and Adverse Clinical Events Post-Percutaneous Coronary Intervention: A Hospital and Primary Care Linked Cohort.,"Harris DE, Lacey A, Akbari A, Obaid DR, Smith DA, Jenkins GH, Barry JP, Gravenor MB, Halcox JP.",,Journal of the American Heart Association,2019,2019-10-29,Y,Adherence; Percutaneous coronary intervention; Clopidogrel; Discontinuation; Discharge Therapy,"Improving Public Health, Understanding the Causes of Disease",,"Background Early discontinuation of P2Y12 antagonists post-percutaneous coronary intervention may increase risk of stent thrombosis or nonstent recurrent myocardial infarction. Our aims were to (1) analyze the early discontinuation rate of P2Y12 antagonists post-percutaneous coronary intervention, (2) explore factors associated with early discontinuation, and (3) analyze the risk of major adverse cardiovascular events (death, acute coronary syndrome, revascularization, or stroke) associated with discontinuation from a prespecified prescribing instruction of 1 year. Method and Results We studied 2090 patients (2011-2015) who were recommended for clopidogrel for 12 months (+aspirin) post-percutaneous coronary intervention within a retrospective observational population cohort. Relationships between clopidogrel discontinuation and major adverse cardiac events were evaluated over 18-month follow-up. Discontinuation of clopidogrel in the first 4 quarters was low at 1.1%, 2.6%, 3.7%, and 6.1%, respectively. Previous revascularization, previous ischemic stroke, and age >80 years were independent predictors of early discontinuation. In a time-dependent multiple regression model, clopidogrel discontinuation and bleeding (hazard ratio=1.82 [1.01-3.30] and hazard ratio=5.30 [3.14-8.94], respectively) were independent predictors of major adverse cardiac events as were age <49 and ≥70 years (versus those aged 50-59 years), hypertension, chronic kidney disease stage 4+, previous revascularization, ischemic stroke, and thromboembolism. Furthermore, in those with both bleeding and clopidogrel discontinuation, hazard ratio for major adverse cardiac events was 9.34 (3.39-25.70). Conclusions Discontinuation of clopidogrel is low in the first year post-percutaneous coronary intervention, where a clear discharge instruction to treat for 1 year is provided. Whereas this is reassuring from the population level, at an individual level discontinuation earlier than the intended duration is associated with an increased rate of adverse events, most notably in those with both bleeding and discontinuation.",,doi:https://doi.org/10.1161/JAHA.119.012812; html:https://europepmc.org/articles/PMC6898825; pdf:https://europepmc.org/articles/PMC6898825?pdf=render 34786063,https://doi.org/,Immune infiltration and prognostic and diagnostic use of LGALS4 in colon adenocarcinoma and bladder urothelial carcinoma.,"Acharjee A, Agarwal P, Nash K, Bano S, Rahman T, Gkoutos GV.",,American journal of translational research,2021,2021-10-15,N,Biomarker; Translational Research; Immune Infiltration; Omics Integration; Blca; Lgals4,,,"Colon adenocarcinoma (COAD) is a common tumor of the gastrointestinal tract with a high mortality rate. Current research has identified many genes associated with immune infiltration that play a vital role in the development of COAD. In this study, we analysed the prognostic and diagnostic features of such immune-related genes in the context of colonic adenocarcinoma (COAD). We analysed 17 overlapping gene expression profiles of COAD and healthy samples obtained from TCGA-COAD and public single-cell sequencing resources, to identify potential therapeutic COAD targets. We evaluated the abundance of immune infiltration with those genes using the TIMER (Tumor Immune Estimation Resource) deconvolution method. Subsequently, we developed predictive and survival models to assess the prognostic value of these genes. The LGALS4 (Galectin-4) gene was found to be significantly (P<0.05) downregulated in COAD and bladder urothelial carcinoma (BLCA) compared to healthy samples. We identified LGALS4 as a prognostic and diagnostic marker for multiple cancer types, including COAD and BLCA. Our analysis reveals a series of novel candidate drug targets, as well as candidate molecular markers, that may explain the pathogenesis of COAD and BLCA. LGALS4 gene is associated with multiple cancer types and is a possible prognostic, as well as diagnostic, marker of COAD and BLCA.",,html:https://europepmc.org/articles/PMC8581917; pdf:https://europepmc.org/articles/PMC8581917?pdf=render -35997000,https://doi.org/10.1111/ene.15530,Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,European journal of neurology,2022,2022-09-11,Y,Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders,,,"

Background and purpose

Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.

Methods

A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.

Results

Individuals with idiopathic dystonia (n = 52,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n = 216,754, 43% vs. 31%, p < 0.001; 45% vs. 37.9%, p < 0.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR] = 1.98, 95% confidence interval [CI] = 1.9-2.1), with an IRR of 12.4 (95% CI = 11.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR = 1.96, 95% CI = 1.85-2.07).

Conclusions

This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",,doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render 35003715,https://doi.org/10.7189/jogh.11.05026,"Uptake, effectiveness and safety of COVID-19 vaccines in children and young people in Scotland: Protocol for early pandemic evaluation and enhanced surveillance of COVID-19 (EAVE II).","Adeloye D, Katikireddi SV, Woolford L, Simpson CR, Shah SA, Agrawal U, Richie LD, Swann OV, Stock SJ, Robertson C, Sheikh A, Rudan I.",,Journal of global health,2021,2021-12-25,Y,,,,"

Background

The dynamics of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and severity of disease among children and young people (CYP) across different settings are of considerable clinical, public health and societal interest. Severe COVID-19 cases, requiring hospitalisations, and deaths have been reported in some CYP suggesting a need to extend vaccinations to these age groups. As part of the ongoing Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study, we aim to investigate the uptake, effectiveness and safety of COVID-19 vaccines in children and young people (CYP) aged 0 to 17 years in Scotland. Specifically, we will estimate: (i) uptake of vaccines against COVID-19, (ii) vaccine effectiveness (VE) against the outcomes of symptomatic SARS-CoV-2 infection, hospitalisation, intensive care unit (ICU) admissions, and death; (iii) VE for first/second dose timing among different age groups and risk groups; and (iv) the safety of vaccines.

Methods and analysis

We will conduct an open prospective cohort study classifying exposure as time-varying. We will compare outcomes amongst first dose vaccinated and second dose vaccinated CYP to those not yet vaccinated. A Test Negative Design (TND) case control study will be nested within this national cohort to investigate VE against symptomatic infection. The primary outcomes will be (i) uptake of vaccines against COVID-19, (ii) time to COVID-19 infection, hospitalisation, ICU admissions or death, and (iii) adverse events related to vaccines. Vaccination status (unvaccinated, one dose and two doses) will be defined as a time-varying exposure. Data from multiple sources will be linked using a unique identifier. We will conduct descriptive analyses to explore trends in vaccine uptake, and association between different exposure variables and vaccine uptake will be determined using multivariable logistic regression models. VE will be assessed from time-dependent Cox models or Poisson regression models, adjusted for relevant confounders, including age, sex, socioeconomic status, and comorbidities. We will employ self-controlled study designs to determine the risk of adverse events following COVID-19 vaccination.

Ethics and dissemination

Ethics approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers.",,doi:https://doi.org/10.7189/jogh.11.05026; html:https://europepmc.org/articles/PMC8709900; pdf:https://europepmc.org/articles/PMC8709900?pdf=render +35997000,https://doi.org/10.1111/ene.15530,Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,European journal of neurology,2022,2022-09-11,Y,Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders,,,"

Background and purpose

Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.

Methods

A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.

Results

Individuals with idiopathic dystonia (n = 52,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n = 216,754, 43% vs. 31%, p < 0.001; 45% vs. 37.9%, p < 0.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR] = 1.98, 95% confidence interval [CI] = 1.9-2.1), with an IRR of 12.4 (95% CI = 11.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR = 1.96, 95% CI = 1.85-2.07).

Conclusions

This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",,doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render 35813279,https://doi.org/10.1016/s2666-7568(22)00147-7,"Duration of vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, and death in residents and staff of long-term care facilities in England (VIVALDI): a prospective cohort study.","Shrotri M, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Giddings R, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(22)00147-7; html:https://europepmc.org/articles/PMC9252508; pdf:https://europepmc.org/articles/PMC9252508?pdf=render 33842409,https://doi.org/10.3389/fped.2021.630036,Microtia: A Data Linkage Study of Epidemiology and Implications for Service Delivery.,"Jovic TH, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Wilson-Jones N, Costello R, Evans P, Cooper M, Key S, Lyons R, Whitaker IS.",,Frontiers in pediatrics,2021,2021-03-26,Y,epidemiology; congenital; Otology; Reconstructive Surgery; Microtia,,,"Introduction: Previous studies of microtia epidemiology globally have demonstrated significant geographical and ethnic variation, cited broadly as affecting 3-5 in 10,000 live births. The aim of this study was to determine the incidence of microtia in a largely homogeneous ethnic population in the United Kingdom (Wales) and to identify factors, such as distance and socioeconomic status, which may influence the access to surgical intervention. Materials and Methods: A retrospective cohort study was conducted using data linkage to identify patients born between 2000 and 2018 with a diagnosis of microtia. Microtia incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Sociodemographic attributes were compared using descriptive statistics to determine differences in access to each type of surgical intervention. Results: A total of 101 patients were identified, 64.4% were male and the median age was 12 (8-16). The mean annual incidence was 2.13 microtia cases per 10,000 births over the 19-year study period. Both temporal and geographic variation was noted. The majority of patients undergoing surgery opted for autologous reconstruction (72.9%) at a median age of 9 (7-10) compared to 7 (5-8) for prosthetic reconstruction. Autologous reconstruction had a higher median number of surgeries (2, 1-3) than prosthetic (1.5, 1-2) and a higher median socioeconomic status of 3 (2-4) compared to 2 (1-4) for the prosthetic cohort. There were no statistically significant differences in the distance traveled for surgery. Discussion: This study highlights a role for data linkage in epidemiological analyses and provides a revised incidence of microtia in Wales. Although the majority of patients opted for autologous reconstruction, demographic disparities in socioeconomic status warrant further investigation, emphasizing the importance of striving for equity in accessibility to surgical intervention.",,doi:https://doi.org/10.3389/fped.2021.630036; html:https://europepmc.org/articles/PMC8033003; pdf:https://europepmc.org/articles/PMC8033003?pdf=render 33901420,https://doi.org/10.1016/s0140-6736(21)00677-2,Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study.,"Vasileiou E, Simpson CR, Shi T, Kerr S, Agrawal U, Akbari A, Bedston S, Beggs J, Bradley D, Chuter A, de Lusignan S, Docherty AB, Ford D, Hobbs FR, Joy M, Katikireddi SV, Marple J, McCowan C, McGagh D, McMenamin J, Moore E, Murray JL, Pan J, Ritchie L, Shah SA, Stock S, Torabi F, Tsang RS, Wood R, Woolhouse M, Robertson C, Sheikh A.",,"Lancet (London, England)",2021,2021-04-23,Y,,,,"

Background

The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.

Methods

We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19-EAVE II-database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1-adjusted rate ratio) following the first dose of vaccine.

Findings

Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID-19 hospital admission at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75-94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72-89 at 28-34 days post-vaccination).

Interpretation

Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding.

Funding

UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.",,doi:https://doi.org/10.1016/S0140-6736(21)00677-2; html:https://europepmc.org/articles/PMC8064669 @@ -442,10 +443,10 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 35749561,https://doi.org/10.1371/journal.pcbi.1010234,"Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study.","Waterlow NR, Toizumi M, van Leeuwen E, Thi Nguyen HA, Myint-Yoshida L, Eggo RM, Flasche S.",,PLoS computational biology,2022,2022-06-24,Y,,,,"Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36-54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1-12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0-11.4); or 16.6 fold (95%CrI 14.5-18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.",,doi:https://doi.org/10.1371/journal.pcbi.1010234; html:https://europepmc.org/articles/PMC9262224; pdf:https://europepmc.org/articles/PMC9262224?pdf=render 34489241,https://doi.org/10.1136/bjsports-2021-104050,Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.,"Walmsley R, Chan S, Smith-Byrne K, Ramakrishnan R, Woodward M, Rahimi K, Dwyer T, Bennett D, Doherty A.",,British journal of sports medicine,2021,2021-09-06,Y,Cardiovascular diseases; Sleep; Methods; Physical Activity; Sedentary Behavior,,,"

Objective

To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.

Methods

Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.

Results

In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.

Conclusion

Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.",,doi:https://doi.org/10.1136/bjsports-2021-104050; html:https://europepmc.org/articles/PMC9484395; pdf:https://europepmc.org/articles/PMC9484395?pdf=render 35868811,https://doi.org/10.1016/s2589-7500(22)00122-4,Data provenance and integrity of health-care systems data for clinical trials.,"Murray ML, Love SB, Carpenter JR, Hartley S, Landray MJ, Mafham M, Parmar MKB, Pinches H, Sydes MR, Healthcare Systems Data for Clinical Trials Collaborative Group.",,The Lancet. Digital health,2022,2022-08-01,Y,,,,,,doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render -34837975,https://doi.org/10.1186/s12885-021-09014-w,Temporality of clinical factors associated with pancreatic cancer: a case-control study using linked electronic health records.,"Dayem Ullah AZM, Stasinos K, Chelala C, Kocher HM.",,BMC cancer,2021,2021-11-27,Y,Risk factor; Pancreatic cancer; Lifestyle; Ethnicity; Comorbidity,,,"

Background

Pancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics.

Methods

We conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models.

Results

We observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer.

Conclusions

Several factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives.",,doi:https://doi.org/10.1186/s12885-021-09014-w; html:https://europepmc.org/articles/PMC8626898; pdf:https://europepmc.org/articles/PMC8626898?pdf=render 33939953,https://doi.org/10.1016/s0140-6736(21)00634-6,"Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.","Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, Eggo RM, Bhaskaran K, Wong AYS, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJW, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B, OpenSAFELY Collaborative.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,"

Background

COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

Methods

We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.

Findings

Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.

Interpretation

Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.

Funding

Medical Research Council.",,doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render -36434299,https://doi.org/10.1007/s00127-022-02393-w,Adverse outcomes associated with recorded victimization in mental health electronic records during the first UK COVID-19 lockdown.,"Kadra-Scalzo G, Kornblum D, Stewart R, Howard LM.",,Social psychiatry and psychiatric epidemiology,2023,2022-11-24,Y,Mental health; Domestic Violence; Victimisation; Adverse Outcomes; Covid-19,,,"

Purpose

The impact of COVID-19 pandemic policies on vulnerable groups such as people with mental health problems who experience violence remains unknown. This study aimed to investigate the prevalence of victimization recorded in mental healthcare records during the first UK lockdown, and associations with subsequent adverse outcomes.

Methods

Using a large mental healthcare database, we identified all adult patients receiving services between 16.12.2019 and 15.06.2020 and extracted records of victimisation between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). We investigated adverse outcomes including acute care, emergency department referrals and all-cause mortality in the year following the lockdown (16.06.2020- 01.11.2021). Multivariable Cox regressions models were constructed, adjusting for socio-demographic, socioeconomic, clinical, and service use factors.

Results

Of 21,037 adults receiving mental healthcare over the observation period, 3,610 (17.2%) had victimisation mentioned between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). Service users with mentions of victimisation in their records had an elevated risk for all outcomes: acute care (adjusted HR: 2.1; 95%CI 1.9-2.3, p < 0.001), emergency department referrals (aHR: 2.0; 95%CI 1.8-2.2; p < 0.001), and all-cause mortality (aHR: 1.5; 95%CI 1.1-1.9; p = 0.003), when compared to service users with no recorded victimisation. We did not observe a statistically significant interaction with gender; however, after adjusting for possible confounders, men had slightly higher hazard ratios for all-cause mortality and emergency department referrals than women.

Conclusion

Patients with documented victimisation during the first UK lockdown were at increased risk for acute care, emergency department referrals and all-cause mortality. Further research is needed into mediating mechanisms.",,doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render +34837975,https://doi.org/10.1186/s12885-021-09014-w,Temporality of clinical factors associated with pancreatic cancer: a case-control study using linked electronic health records.,"Dayem Ullah AZM, Stasinos K, Chelala C, Kocher HM.",,BMC cancer,2021,2021-11-27,Y,Risk factor; Pancreatic cancer; Lifestyle; Ethnicity; Comorbidity,,,"

Background

Pancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics.

Methods

We conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models.

Results

We observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer.

Conclusions

Several factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives.",,doi:https://doi.org/10.1186/s12885-021-09014-w; html:https://europepmc.org/articles/PMC8626898; pdf:https://europepmc.org/articles/PMC8626898?pdf=render 33644411,https://doi.org/10.23889/ijpds.v5i1.1346,Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales: A Retrospective Review.,"Griffiths R, Schlüter DK, Akbari A, Cosgriff R, Tucker D, Taylor-Robinson D.",,International journal of population data science,2020,2020-08-11,Y,,,,"

Introduction

The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry.

Objectives

To establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research.

Methods

Three EHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications.

Results

We identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source.

Conclusion

Identifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.",,doi:https://doi.org/10.23889/ijpds.v5i1.1346; html:https://europepmc.org/articles/PMC7898022; pdf:https://europepmc.org/articles/PMC7898022?pdf=render +36434299,https://doi.org/10.1007/s00127-022-02393-w,Adverse outcomes associated with recorded victimization in mental health electronic records during the first UK COVID-19 lockdown.,"Kadra-Scalzo G, Kornblum D, Stewart R, Howard LM.",,Social psychiatry and psychiatric epidemiology,2023,2022-11-24,Y,Mental health; Domestic Violence; Victimisation; Adverse Outcomes; Covid-19,,,"

Purpose

The impact of COVID-19 pandemic policies on vulnerable groups such as people with mental health problems who experience violence remains unknown. This study aimed to investigate the prevalence of victimization recorded in mental healthcare records during the first UK lockdown, and associations with subsequent adverse outcomes.

Methods

Using a large mental healthcare database, we identified all adult patients receiving services between 16.12.2019 and 15.06.2020 and extracted records of victimisation between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). We investigated adverse outcomes including acute care, emergency department referrals and all-cause mortality in the year following the lockdown (16.06.2020- 01.11.2021). Multivariable Cox regressions models were constructed, adjusting for socio-demographic, socioeconomic, clinical, and service use factors.

Results

Of 21,037 adults receiving mental healthcare over the observation period, 3,610 (17.2%) had victimisation mentioned between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). Service users with mentions of victimisation in their records had an elevated risk for all outcomes: acute care (adjusted HR: 2.1; 95%CI 1.9-2.3, p < 0.001), emergency department referrals (aHR: 2.0; 95%CI 1.8-2.2; p < 0.001), and all-cause mortality (aHR: 1.5; 95%CI 1.1-1.9; p = 0.003), when compared to service users with no recorded victimisation. We did not observe a statistically significant interaction with gender; however, after adjusting for possible confounders, men had slightly higher hazard ratios for all-cause mortality and emergency department referrals than women.

Conclusion

Patients with documented victimisation during the first UK lockdown were at increased risk for acute care, emergency department referrals and all-cause mortality. Further research is needed into mediating mechanisms.",,doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render 33965593,https://doi.org/10.1016/j.jaip.2021.04.055,Intolerance to Angiotensin Converting Enzyme Inhibitors in Asthma and the General Population: A UK Population-Based Cohort Study.,"Morales DR, Lipworth BJ, Donnan PT, Wang H.",,The journal of allergy and clinical immunology. In practice,2021,2021-05-06,Y,Hypertension; Angiotensin converting enzyme; Asthma; epidemiology; Cough,,,"

Background

Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). Angiotensin converting enzyme inhibitor intolerance may be mediated by bradykinin, potentially affecting airway hyperresponsiveness.

Objective

To assess the risk for switching to ARBs in asthma.

Methods

We conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population was compared. Adjusted hazard ratios (HRs) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type.

Results

Of 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR = 1.16; 95% confidence interval [CI], 1.14-1.18; P ≤ .001) and highest in those at BTS step 3 or greater (HR = 1.35, 95% CI, 1.32-1.39; and HR = 1.18, 95% CI, 1.15-1.22, P ≤ .001 for patients aged ≥60 and <60 years, respectively). Hazard was highest with enalapril (HR = 1.25, 95% CI, 1.18-1.34, P ≤ .001; HR = 1.44, 95% CI, 1.32-1.58, P ≤ .001 for BTS step 3 or greater asthma). No increased hazard was observed in chronic obstructive pulmonary disease or those younger than age 60 years at BTS step 1/2. The number needed to treat varied by age, sex, and body mass index (BMI), ranging between 21 and 4, and was lowest in older women with a BMI of 25 or greater.

Conclusions

People with active asthma are more likely to switch to ARBs after commencing ACEI therapy. The number needed to treat varies by age, sex, BMI, and BTS step. Angiotensin-II receptor blocker could potentially be considered first-line in people with asthma and in those with high-risk characteristics.",,doi:https://doi.org/10.1016/j.jaip.2021.04.055; html:https://europepmc.org/articles/PMC8443840; pdf:https://europepmc.org/articles/PMC8443840?pdf=render 34389694,https://doi.org/10.1158/1535-7163.mct-20-1050,Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer.,"Crawford N, Stott KJ, Sessler T, McCann C, McDaid W, Lees A, Latimer C, Fox JP, Munck JM, Smyth T, Shah A, Martins V, Lawler M, Dunne PD, Kerr EM, McDade SS, Coyle VM, Longley DB.",,Molecular cancer therapeutics,2021,2021-08-13,Y,,,,"Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)-based adjuvant chemotherapy, suggesting their involvement in promoting chemoresistance. A novel IAP antagonist tolinapant (ASTX660) potently and rapidly downregulated cIAP1 in colorectal cancer models, demonstrating its robust on-target efficacy. In cells co-cultured with TNFα to mimic an inflammatory tumor microenvironment, tolinapant induced caspase-8-dependent apoptosis in colorectal cancer cell line models; however, the extent of apoptosis was limited because of inhibition by the caspase-8 paralogs FLIP and, unexpectedly, caspase-10. Importantly, tolinapant-induced apoptosis was augmented by FOLFOX in human colorectal cancer and murine organoid models in vitro and in vivo, due (at least in part) to FOLFOX-induced downregulation of class I histone deacetylases (HDAC), leading to acetylation of the FLIP-binding partner Ku70 and downregulation of FLIP. Moreover, the effects of FOLFOX could be phenocopied using the clinically relevant class I HDAC inhibitor, entinostat, which also induced acetylation of Ku70 and FLIP downregulation. Further analyses revealed that caspase-8 knockout RIPK3-positive colorectal cancer models were sensitive to tolinapant-induced necroptosis, an effect that could be exploited in caspase-8-proficient models using the clinically relevant caspase inhibitor emricasan. Our study provides evidence for immediate clinical exploration of tolinapant in combination with FOLFOX in poor prognosis MSS colorectal cancer with elevated cIAP1/2 expression.",,doi:https://doi.org/10.1158/1535-7163.MCT-20-1050; html:https://europepmc.org/articles/PMC7611622; pdf:https://europepmc.org/articles/PMC7611622?pdf=render 37004203,https://doi.org/10.1093/qjmed/hcad050,Classifying the unclassifiable-a Delphi study to reach consensus on the fibrotic nature of diseases.,"Massen GM, Allen RJ, Leavy OC, Selby NM, Aithal GP, Oliver N, Parfrey H, Wain LV, Jenkins G, Stewart I, Quint JK.",,QJM : monthly journal of the Association of Physicians,2023,2023-06-01,Y,,,,"

Background

Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity.

Aim

A Delphi study was performed to reach consensus on which diseases may be described as fibrotic.

Methods

Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as 'fibrotic manifestation always present', 'can develop fibrotic manifestations', 'associated with fibrotic manifestations' or 'not fibrotic nor associated'. Classifications of 'fibrotic manifestation always present' and 'can develop fibrotic manifestations' were merged and termed 'fibrotic'. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification.

Results

After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement.

Conclusion

Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.",,doi:https://doi.org/10.1093/qjmed/hcad050; html:https://europepmc.org/articles/PMC10250078; pdf:https://europepmc.org/articles/PMC10250078?pdf=render; pdf:https://academic.oup.com/qjmed/advance-article-pdf/doi/10.1093/qjmed/hcad050/50051055/hcad050.pdf @@ -455,22 +456,22 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 33801002,https://doi.org/10.3390/s21062190,A Novel Coupled Reaction-Diffusion System for Explainable Gene Expression Profiling. ,"Farouq MW, Boulila W, Hussain Z, Rashid A, Shah M, Hussain S, Ng N, Ng D, Hanif H, Shaikh MG, Sheikh A, Hussain A.",,"Sensors (Basel, Switzerland)",2021,2021-03-21,Y,,,,"Machine learning (ML)-based algorithms are playing an important role in cancer diagnosis and are increasingly being used to aid clinical decision-making. However, these commonly operate as 'black boxes' and it is unclear how decisions are derived. Recently, techniques have been applied to help us understand how specific ML models work and explain the rational for outputs. This study aims to determine why a given type of cancer has a certain phenotypic characteristic. Cancer results in cellular dysregulation and a thorough consideration of cancer regulators is required. This would increase our understanding of the nature of the disease and help discover more effective diagnostic, prognostic, and treatment methods for a variety of cancer types and stages. Our study proposes a novel explainable analysis of potential biomarkers denoting tumorigenesis in non-small cell lung cancer. A number of these biomarkers are known to appear following various treatment pathways. An enhanced analysis is enabled through a novel mathematical formulation for the regulators of mRNA, the regulators of ncRNA, and the coupled mRNA-ncRNA regulators. Temporal gene expression profiles are approximated in a two-dimensional spatial domain for the transition states before converging to the stationary state, using a system comprised of coupled-reaction partial differential equations. Simulation experiments demonstrate that the proposed mathematical gene-expression profile represents a best fit for the population abundance of these oncogenes. In future, our proposed solution can lead to the development of alternative interpretable approaches, through the application of ML models to discover unknown dynamics in gene regulatory systems.",,doi:https://doi.org/10.3390/s21062190; html:https://europepmc.org/articles/PMC8003942; pdf:https://europepmc.org/articles/PMC8003942?pdf=render 32463370,https://doi.org/10.2196/16452,Challenges of Clustering Multimodal Clinical Data: Review of Applications in Asthma Subtyping.,"Horne E, Tibble H, Sheikh A, Tsanas A.",,JMIR medical informatics,2020,2020-05-28,Y,Cluster analysis; Asthma; data mining; Machine Learning; Unsupervised Machine Learning,,,"

Background

In the current era of personalized medicine, there is increasing interest in understanding the heterogeneity in disease populations. Cluster analysis is a method commonly used to identify subtypes in heterogeneous disease populations. The clinical data used in such applications are typically multimodal, which can make the application of traditional cluster analysis methods challenging.

Objective

This study aimed to review the research literature on the application of clustering multimodal clinical data to identify asthma subtypes. We assessed common problems and shortcomings in the application of cluster analysis methods in determining asthma subtypes, such that they can be brought to the attention of the research community and avoided in future studies.

Methods

We searched PubMed and Scopus bibliographic databases with terms related to cluster analysis and asthma to identify studies that applied dissimilarity-based cluster analysis methods. We recorded the analytic methods used in each study at each step of the cluster analysis process.

Results

Our literature search identified 63 studies that applied cluster analysis to multimodal clinical data to identify asthma subtypes. The features fed into the cluster algorithms were of a mixed type in 47 (75%) studies and continuous in 12 (19%), and the feature type was unclear in the remaining 4 (6%) studies. A total of 23 (37%) studies used hierarchical clustering with Ward linkage, and 22 (35%) studies used k-means clustering. Of these 45 studies, 39 had mixed-type features, but only 5 specified dissimilarity measures that could handle mixed-type features. A further 9 (14%) studies used a preclustering step to create small clusters to feed on a hierarchical method. The original sample sizes in these 9 studies ranged from 84 to 349. The remaining studies used hierarchical clustering with other linkages (n=3), medoid-based methods (n=3), spectral clustering (n=1), and multiple kernel k-means clustering (n=1), and in 1 study, the methods were unclear. Of 63 studies, 54 (86%) explained the methods used to determine the number of clusters, 24 (38%) studies tested the quality of their cluster solution, and 11 (17%) studies tested the stability of their solution. Reporting of the cluster analysis was generally poor in terms of the methods employed and their justification.

Conclusions

This review highlights common issues in the application of cluster analysis to multimodal clinical data to identify asthma subtypes. Some of these issues were related to the multimodal nature of the data, but many were more general issues in the application of cluster analysis. Although cluster analysis may be a useful tool for investigating disease subtypes, we recommend that future studies carefully consider the implications of clustering multimodal data, the cluster analysis process itself, and the reporting of methods to facilitate replication and interpretation of findings.",,doi:https://doi.org/10.2196/16452; html:https://europepmc.org/articles/PMC7290450 37478175,https://doi.org/10.1126/sciadv.adh8839,Citizen science reveals landscape-scale exposures to multiazole-resistant Aspergillus fumigatus bioaerosols.,"Shelton JMG, Rhodes J, Uzzell CB, Hemmings S, Brackin AP, Sewell TR, Alghamdi A, Dyer PS, Fraser M, Borman AM, Johnson EM, Piel FB, Singer AC, Fisher MC.",,Science advances,2023,2023-07-21,Y,,,,"Using a citizen science approach, we identify a country-wide exposure to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to the agricultural fungicide tebuconazole and first-line azole clinical antifungal drugs. Genomic analysis shows no distinction between resistant genotypes found in the environment and in patients, indicating that at least 40% of azole-resistant A. fumigatus infections are acquired from environmental exposures. Hotspots and coldspots of aerosolized azole-resistant spores were not stable between seasonal sampling periods. This suggests a high degree of atmospheric mixing resulting in an estimated per capita cumulative annual exposure of 21 days (±2.6). Because of the ubiquity of this measured exposure, it is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis.",,doi:https://doi.org/10.1126/sciadv.adh8839; html:https://europepmc.org/articles/PMC10361594; pdf:https://europepmc.org/articles/PMC10361594?pdf=render -34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render +34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render; pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3 37398988,https://doi.org/10.1007/s40258-023-00821-9,Correction to: The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.,"Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.",,Applied health economics and health policy,2023,2023-09-01,Y,,,,,,doi:https://doi.org/10.1007/s40258-023-00821-9; html:https://europepmc.org/articles/PMC10403424; pdf:https://europepmc.org/articles/PMC10403424?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s40258-023-00821-9.pdf 31462651,https://doi.org/10.1038/s41598-019-48927-2,Hierarchical Template Matching for 3D Myocardial Tracking and Cardiac Strain Estimation.,"Bhalodiya JM, Palit A, Ferrante E, Tiwari MK, Bhudia SK, Arvanitis TN, Williams MA.",,Scientific reports,2019,2019-08-28,Y,,Applied Analytics,,"Myocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers.",,doi:https://doi.org/10.1038/s41598-019-48927-2; html:https://europepmc.org/articles/PMC6713749; pdf:https://europepmc.org/articles/PMC6713749?pdf=render 36713473,https://doi.org/10.1093/ofid/ofac694,Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).,"Stirrup O, Shrotri M, Adams NL, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,Open forum infectious diseases,2023,2022-12-29,Y,Vaccine Effectiveness; Long-term Care Facilities; Covid-19; Sars-cov-2; Omicron,,,"

Background

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

Methods

We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021-March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence.

Results

A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths.

Conclusions

Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.",,doi:https://doi.org/10.1093/ofid/ofac694; html:https://europepmc.org/articles/PMC9874026; pdf:https://europepmc.org/articles/PMC9874026?pdf=render -35067242,https://doi.org/10.1192/bjp.2021.219,Prediction models in first-episode psychosis: systematic review and critical appraisal.,"Lee R, Leighton SP, Thomas L, Gkoutos GV, Wood SJ, Fenton SH, Deligianni F, Cavanagh J, Mallikarjun PK.",,The British journal of psychiatry : the journal of mental science,2022,2022-01-24,N,Prediction; Schizophrenia; Psychotic Disorders; Outcome Studies; Precision Medicine,,,"

Background

People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.

Aims

We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.

Method

A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.

Results

Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.

Conclusions

Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.",,doi:https://doi.org/10.1192/bjp.2021.219; html:https://europepmc.org/articles/PMC7612705; pdf:https://europepmc.org/articles/PMC7612705?pdf=render; doi:https://doi.org/10.1192/bjp.2021.219 33419870,https://doi.org/10.1136/bmjhci-2020-100254,Network graph representation of COVID-19 scientific publications to aid knowledge discovery. ,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,BMJ health & care informatics,2021,2021-01-01,Y,,,,"Numerous scientific journal articles related to COVID-19 have been rapidly published, making navigation and understanding of relationships difficult. A graph network was constructed from the publicly available COVID-19 Open Research Dataset (CORD-19) of COVID-19-related publications using an engine leveraging medical knowledge bases to identify discrete medical concepts and an open-source tool (Gephi) to visualise the network. The network shows connections between diseases, medications and procedures identified from the title and abstract of 195 958 COVID-19-related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledge base and the size of the node related to the number of publications containing the term. The data set and visualisations were made publicly accessible via a webtool. Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity inter-relationships to improve understanding of diseases such as COVID-19.",,doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render 33623985,https://doi.org/10.1093/cid/ciab159,Shorter and Longer Courses of Antibiotics for Common Infections and the Association With Reductions of Infection-Related Complications Including Hospital Admissions.,"Palin V, Welfare W, Ashcroft DM, van Staa TP.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2021,2021-11-01,Y,Antibiotics; Antimicrobial resistance; Antibiotic Duration; Infection Complication,,,"

Background

Antimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications.

Methods

Clinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014-June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations.

Results

The duration of antibiotic courses increased over the study period (5.2-19.1%); 6-7 days were most common (66.9%). Most infection-related hospitalizations occurred with prescriptions of 8-15 days (0.21%), accompanied by greater risk of infection-related complications compared to patients who received a short prescription (HR: 1.75 [95% CI: 1.54-2.00]). Comparing HRs in the first 5 days versus remaining follow-up showed longer antibiotic courses were no more effective than shorter courses (1.02 [95% CI: 0.90-1.16] and 0.92 [95% CI: 0.75-1.12]). No variation by infection-type was observed.

Conclusions

Equal effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history.SummaryPrescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses.",,doi:https://doi.org/10.1093/cid/ciab159; html:https://europepmc.org/articles/PMC8599204; pdf:https://europepmc.org/articles/PMC8599204?pdf=render +35067242,https://doi.org/10.1192/bjp.2021.219,Prediction models in first-episode psychosis: systematic review and critical appraisal.,"Lee R, Leighton SP, Thomas L, Gkoutos GV, Wood SJ, Fenton SH, Deligianni F, Cavanagh J, Mallikarjun PK.",,The British journal of psychiatry : the journal of mental science,2022,2022-01-24,N,Prediction; Schizophrenia; Psychotic Disorders; Outcome Studies; Precision Medicine,,,"

Background

People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.

Aims

We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.

Method

A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.

Results

Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.

Conclusions

Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.",,doi:https://doi.org/10.1192/bjp.2021.219; html:https://europepmc.org/articles/PMC7612705; pdf:https://europepmc.org/articles/PMC7612705?pdf=render; doi:https://doi.org/10.1192/bjp.2021.219 33495722,https://doi.org/10.1109/access.2021.3050524,Remote Assessment of Parkinson's Disease Symptom Severity Using the Simulated Cellular Mobile Telephone Network.,"Tsanas A, Little MA, Ramig LO.",,"IEEE access : practical innovations, open solutions",2021,2021-01-11,Y,Telemedicine; Parkinson’s Disease; Decision Support Tool; Nonlinear Speech Signal Processing,,,"Telemonitoring of Parkinson's Disease (PD) has attracted considerable research interest because of its potential to make a lasting, positive impact on the life of patients and their carers. Purpose-built devices have been developed that record various signals which can be associated with average PD symptom severity, as quantified on standard clinical metrics such as the Unified Parkinson's Disease Rating Scale (UPDRS). Speech signals are particularly promising in this regard, because they can be easily recorded without the use of expensive, dedicated hardware. Previous studies have demonstrated replication of UPDRS to within less than 2 points of a clinical raters' assessment of symptom severity, using high-quality speech signals collected using dedicated telemonitoring hardware. Here, we investigate the potential of using the standard voice-over-GSM (2G) or UMTS (3G) cellular mobile telephone networks for PD telemonitoring, networks that, together, have greater than 5 billion subscribers worldwide. We test the robustness of this approach using a simulated noisy mobile communication network over which speech signals are transmitted, and approximately 6000 recordings from 42 PD subjects. We show that UPDRS can be estimated to within less than 3.5 points difference from the clinical raters' assessment, which is clinically useful given that the inter-rater variability for UPDRS can be as high as 4-5 UPDRS points. This provides compelling evidence that the existing voice telephone network has potential towards facilitating inexpensive, mass-scale PD symptom telemonitoring applications.",,doi:https://doi.org/10.1109/ACCESS.2021.3050524; html:https://europepmc.org/articles/PMC7821632; pdf:https://europepmc.org/articles/PMC7821632?pdf=render 35953587,https://doi.org/10.1038/s41588-022-01153-5,A multi-tissue atlas of regulatory variants in cattle.,"Liu S, Gao Y, Canela-Xandri O, Wang S, Yu Y, Cai W, Li B, Xiang R, Chamberlain AJ, Pairo-Castineira E, D'Mellow K, Rawlik K, Xia C, Yao Y, Navarro P, Rocha D, Li X, Yan Z, Li C, Rosen BD, Van Tassell CP, Vanraden PM, Zhang S, Ma L, Cole JB, Liu GE, Tenesa A, Fang L.",,Nature genetics,2022,2022-08-11,Y,,,,"Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype-Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.",,doi:https://doi.org/10.1038/s41588-022-01153-5; html:https://europepmc.org/articles/PMC7613894; pdf:https://europepmc.org/articles/PMC7613894?pdf=render 34431993,https://doi.org/10.1093/eurheartj/ehab581,Risk factors for type 1 and type 2 myocardial infarction.,"Wereski R, Kimenai DM, Bularga A, Taggart C, Lowe DJ, Mills NL, Chapman AR.",,European heart journal,2022,2022-01-01,Y,Myocardial infarction; acute coronary syndrome; type 2; risk factors; Universal Definition,,,"

Aims

Whilst the risk factors for type 1 myocardial infarction due to atherosclerotic plaque rupture and thrombosis are established, our understanding of the factors that predispose to type 2 myocardial infarction during acute illness is still emerging. Our aim was to evaluate and compare the risk factors for type 1 and type 2 myocardial infarction.

Methods and results

We conducted a secondary analysis of a multi-centre randomized trial population of 48 282 consecutive patients attending hospital with suspected acute coronary syndrome. The diagnosis of myocardial infarction during the index presentation and all subsequent reattendances was adjudicated according to the Universal Definition of Myocardial Infarction. Cox regression was used to identify predictors of future type 1 and type 2 myocardial infarction during a 1-year follow-up period. Within 1 year, 1331 patients had a subsequent myocardial infarction, with 924 and 407 adjudicated as type 1 and type 2 myocardial infarction, respectively. Risk factors for type 1 and type 2 myocardial infarction were similar, with age, hyperlipidaemia, diabetes, abnormal renal function, and known coronary disease predictors for both (P < 0.05 for all). Whilst women accounted for a greater proportion of patients with type 2 as compared to type 1 myocardial infarction, after adjustment for other risk factors, sex was not a predictor of type 2 myocardial events [adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.66-1.01]. The strongest predictor of type 2 myocardial infarction was a prior history of type 2 events (aHR 6.18, 95% CI 4.70-8.12).

Conclusions

Risk factors for coronary disease that are associated with type 1 myocardial infarction are also important predictors of type 2 events during acute illness. Treatment of these risk factors may reduce future risk of both type 1 and type 2 myocardial infarction.",,doi:https://doi.org/10.1093/eurheartj/ehab581; html:https://europepmc.org/articles/PMC8757580; pdf:https://europepmc.org/articles/PMC8757580?pdf=render 34518162,https://doi.org/10.1136/bjophthalmol-2021-319383,Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.,"Mollan SP, Fu DJ, Chuo CY, Gannon JG, Lee WH, Hopkins JJ, Hughes C, Denniston AK, Keane PA, Cantrell R.",,The British journal of ophthalmology,2023,2021-09-13,Y,Clinical Trial; Neovascularisation; Covid-19,,,"

Objective

Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.

Methods and analysis

This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).

Results

At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.

Conclusions

Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.

Trial registration number

NCT00056836.",,doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?pdf=render 36720882,https://doi.org/10.1038/s41597-023-01949-y,"Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants.","Ritchie SC, Surendran P, Karthikeyan S, Lambert SA, Bolton T, Pennells L, Danesh J, Di Angelantonio E, Butterworth AS, Inouye M.",,Scientific data,2023,2023-01-31,Y,,,,"Metabolic biomarker data quantified by nuclear magnetic resonance (NMR) spectroscopy in approximately 121,000 UK Biobank participants has recently been released as a community resource, comprising absolute concentrations and ratios of 249 circulating metabolites, lipids, and lipoprotein sub-fractions. Here we identify and characterise additional sources of unwanted technical variation influencing individual biomarkers in the data available to download from UK Biobank. These included sample preparation time, shipping plate well, spectrometer batch effects, drift over time within spectrometer, and outlier shipping plates. We developed a procedure for removing this unwanted technical variation, and demonstrate that it increases signal for genetic and epidemiological studies of the NMR metabolic biomarker data in UK Biobank. We subsequently developed an R package, ukbnmr, which we make available to the wider research community to enhance the utility of the UK Biobank NMR metabolic biomarker data and to facilitate rapid analysis.",,doi:https://doi.org/10.1038/s41597-023-01949-y; html:https://europepmc.org/articles/PMC9887579; pdf:https://europepmc.org/articles/PMC9887579?pdf=render -35534084,https://doi.org/10.1136/bmjopen-2021-054186,Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.,"Gordon B, Fennessy C, Varma S, Barrett J, McCondochie E, Heritage T, Duroe O, Jeffery R, Rajamani V, Earlam K, Banda V, Sebire N.",,BMJ open,2022,2022-05-09,Y,Information management; information technology; Health Informatics,,,"

Objectives

To objectively evaluate freely available data profiling software tools using healthcare data.

Design

Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset.

Setting

Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise.

Participants

28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients.

Results

Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics.

Conclusions

Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.",,doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render 34164795,https://doi.org/10.1007/s40801-021-00256-5,Associations Between Anticholinergic Medication Exposure and Adverse Health Outcomes in Older People with Frailty: A Systematic Review and Meta-analysis.,"Mehdizadeh D, Hale M, Todd O, Zaman H, Marques I, Petty D, Alldred DP, Johnson O, Faisal M, Gardner P, Clegg A.",,Drugs - real world outcomes,2021,2021-06-23,Y,,,,"

Introduction

There are robust associations between use of anticholinergic medicines and adverse effects in older people. However, the nature of these associations for older people living with frailty is yet to be established.

Objectives

The aims were to identify and investigate associations between anticholinergics and adverse outcomes in older people living with frailty and to investigate whether exposure is associated with greater risks according to frailty status.

Methods

MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Web of Science and PsycINFO were searched to 1 August 2019. Observational studies reporting associations between anticholinergics and outcomes in older adults (average age ≥ 65 years) that reported frailty using validated measures were included. Primary outcomes were physical impairment, cognitive dysfunction, and change in frailty status. Risk of bias was evaluated using the Cochrane Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken where appropriate.

Results

Thirteen studies (21,516 participants) were included (ten community, one residential aged-care facility and two hospital studies). Observed associations included reduced ability for chair standing, slower gait speeds, poorer physical performance, increased risk of falls and mortality. Conflicting results were reported for grip strength, timed up and go test, cognition and activities of daily living. No associations were observed for transitions between frailty states, psychological wellbeing or benzodiazepine-related adverse reactions. There was no clear evidence of differences in risks according to frailty status.

Conclusions

Anticholinergics are associated with adverse outcomes in older people living with frailty; however, the literature has significant methodological limitations. There is insufficient evidence to suggest greater risks based on frailty, and there is an urgent need to evaluate this further in well-designed studies stratifying by frailty.",,doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf -35958702,https://doi.org/10.1007/s40653-021-00433-2,The Secondary Harms of Parental Substance Use on Children's Educational Outcomes: A Review.,Lowthian E.,,Journal of child & adolescent trauma,2022,2022-01-14,Y,Drugs; Review; Alcohol; Education; Parental Substance Use,,,"Parental substance use, that is alcohol and illicit drugs, can have a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current reviews of the literature in the field of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's educational attainment. To grasp the available literature, the method from Arksey and O'Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children's school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children's educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.",,doi:https://doi.org/10.1007/s40653-021-00433-2; html:https://europepmc.org/articles/PMC9360289; pdf:https://europepmc.org/articles/PMC9360289?pdf=render +35534084,https://doi.org/10.1136/bmjopen-2021-054186,Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.,"Gordon B, Fennessy C, Varma S, Barrett J, McCondochie E, Heritage T, Duroe O, Jeffery R, Rajamani V, Earlam K, Banda V, Sebire N.",,BMJ open,2022,2022-05-09,Y,Information management; information technology; Health Informatics,,,"

Objectives

To objectively evaluate freely available data profiling software tools using healthcare data.

Design

Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset.

Setting

Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise.

Participants

28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients.

Results

Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics.

Conclusions

Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.",,doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render 31591592,https://doi.org/10.1038/s41591-019-0597-x,Avoidable flaws in observational analyses: an application to statins and cancer.,"Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA.",,Nature medicine,2019,2019-10-07,N,,,,"The increasing availability of large healthcare databases is fueling an intense debate on whether real-world data should play a role in the assessment of the benefit-risk of medical treatments. In many observational studies, for example, statin users were found to have a substantially lower risk of cancer than in meta-analyses of randomized trials. Although such discrepancies are often attributed to a lack of randomization in the observational studies, they might be explained by flaws that can be avoided by explicitly emulating a target trial (the randomized trial that would answer the question of interest). Using the electronic health records of 733,804 UK adults, we emulated a target trial of statins and cancer and compared our estimates with those obtained using previously applied analytic approaches. Over the 10-yr follow-up, 28,408 individuals developed cancer. Under the target trial approach, estimated observational analogs of intention-to-treat and per-protocol 10-yr cancer-free survival differences were -0.5% (95% confidence interval (CI) -1.0%, 0.0%) and -0.3% (95% CI -1.5%, 0.5%), respectively. By contrast, previous analytic approaches yielded estimates that appeared to be strongly protective. Our findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses.",,doi:https://doi.org/10.1038/s41591-019-0597-x; html:https://europepmc.org/articles/PMC7076561; pdf:https://europepmc.org/articles/PMC7076561?pdf=render; doi:https://doi.org/10.1038/s41591-019-0597-x +35958702,https://doi.org/10.1007/s40653-021-00433-2,The Secondary Harms of Parental Substance Use on Children's Educational Outcomes: A Review.,Lowthian E.,,Journal of child & adolescent trauma,2022,2022-01-14,Y,Drugs; Review; Alcohol; Education; Parental Substance Use,,,"Parental substance use, that is alcohol and illicit drugs, can have a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current reviews of the literature in the field of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's educational attainment. To grasp the available literature, the method from Arksey and O'Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children's school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children's educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.",,doi:https://doi.org/10.1007/s40653-021-00433-2; html:https://europepmc.org/articles/PMC9360289; pdf:https://europepmc.org/articles/PMC9360289?pdf=render 37649988,https://doi.org/10.1093/jamiaopen/ooad078,"Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists. ","Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.",,JAMIA open,2023,2023-08-29,N,,,,"To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases. We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335 931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables. In Search A, we identified 165 150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317 963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19 696 prescriptions; C:1145) and SAMA inhalers (A and B:35 310; C:564). We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses. Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.",,doi:https://doi.org/10.1093/jamiaopen/ooad078 35962974,https://doi.org/10.1093/ije/dyac158,Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform.,"Wing K, Grint DJ, Mathur R, Gibbs HP, Hickman G, Nightingale E, Schultze A, Forbes H, Nafilyan V, Bhaskaran K, Williamson E, House T, Pellis L, Herrett E, Gautam N, Curtis HJ, Rentsch CT, Wong AYS, MacKenna B, Mehrkar A, Bacon S, Douglas IJ, Evans SJW, Tomlinson L, Goldacre B, Eggo RM.",,International journal of epidemiology,2022,2022-12-01,Y,Household; Older People; Ethnicity; Deprivation; Comorbidities; Multigenerational; Population-level; Covid-19; Opensafely,,,"

Background

Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older individuals.

Methods

With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of age-based generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in Wave 1 (1 February 2020-31 August 2020) and 2 731 427 in Wave 2 (1 September 2020-31 January 2021).

Results

Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves [e.g. Wave 2, 67+ living with three other generations vs 67+-year-olds only: White hazard ratio (HR) 1.61 95% CI 1.38-1.87, South Asian HR 1.76 95% CI 1.48-2.10], with a trend for increased risks of severe COVID-19 with increasing generations in Wave 2. There was also an increased risk of severe COVID-19 in Wave 1 associated with living alone for White (HR 1.35 95% CI 1.30-1.41), South Asian (HR 1.47 95% CI 1.18-1.84) and Other (HR 1.72 95% CI 0.99-2.97) ethnicities, an effect that persisted for White older people in Wave 2.

Conclusions

Both multigenerational living and living alone were associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings, whereas a substantial proportion of White older people live alone. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics.",,doi:https://doi.org/10.1093/ije/dyac158; html:https://europepmc.org/articles/PMC9384728; pdf:https://europepmc.org/articles/PMC9384728?pdf=render 35954935,https://doi.org/10.3390/ijerph19159578,Comparing Peak Burn Injury Times and Characteristics in Australia and New Zealand.,"Hong R, Perkins M, Gabbe BJ, Tracy LM.",,International journal of environmental research and public health,2022,2022-08-04,Y,Burns; Cooking; Registry; scald; Flame,,,"Burns are a leading cause of morbidity and mortality worldwide. Understanding when and how burns occur, as well as the differences between countries, would aid prevention efforts. A review of burn injuries occurring between July 2009 and June 2021 was undertaken using data from the Burns Registry of Australia and New Zealand. Peak injury times were identified on a country-by-country basis. Variations in demographic and injury event profiles between countries were compared using descriptive statistics. There were 26,925 admissions recorded across the two countries (23,323 for Australia; 3602 for New Zealand). The greatest number of injuries occurred between 6 PM to 7 PM in Australia (1871, 8.0%) and between 5 PM to 6 PM in New Zealand (280, 7.8%). In both countries, scalds accounted for the greatest proportion of injuries during peak times (988, 45.8%), but a greater proportion of young children (under three years) sustained burns during New Zealand's peak times. The number of burn injuries associated with the preparation and/or consumption of food offers an opportunity for a targeted prevention program that may yield benefits across the two countries. Age- and mechanism-related differences in the profile of burn-injured patients need to be considered when developing and implementing such a program.",,doi:https://doi.org/10.3390/ijerph19159578; html:https://europepmc.org/articles/PMC9368485; pdf:https://europepmc.org/articles/PMC9368485?pdf=render @@ -482,24 +483,24 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 33739254,https://doi.org/10.2807/1560-7917.es.2021.26.11.2100256,"Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February.","Grint DJ, Wing K, Williamson E, McDonald HI, Bhaskaran K, Evans D, Evans SJ, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AY, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, Blomquist P, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Goldacre B, Smeeth L, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-03-01,Y,Mortality; Coronavirus; Cfr; Case Fatality Risk; Covid-19; Sars-cov-2; Variant Of Concern,,,The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.,,doi:https://doi.org/10.2807/1560-7917.ES.2021.26.11.2100256; html:https://europepmc.org/articles/PMC7976383; pdf:https://europepmc.org/articles/PMC7976383?pdf=render 34308125,https://doi.org/10.1136/bmjnph-2020-000225,Effect of ultraprocessed food intake on cardiometabolic risk is mediated by diet quality: a cross-sectional study.,"Griffin J, Albaloul A, Kopytek A, Elliott P, Frost G.",,"BMJ nutrition, prevention & health",2021,2021-04-07,Y,metabolic syndrome; Dietary Patterns,,,"

Objective

To examine the effect of the consumption of ultraprocessed food on diet quality, and cardiometabolic risk (CMR) in an occupational cohort.

Design

Cross-sectional.

Setting

Occupational cohort.

Participants

53 163 British police force employees enrolled (2004-2012) into the Airwave Health Monitoring Study. A total of 28 forces across the UK agreed to participate. 9009 participants with available 7-day diet record data and complete co-variate data are reported in this study.

Main outcome measures

A CMR and Dietary Approaches to Stop Hypertension score were treated as continuous variables and used to generate measures of cardiometabolic health and diet quality. Secondary outcome measures include percentage of energy from fat, saturated fat, carbohydrate, protein and non-milk extrinsic sugars (NMES) and fibre grams per 1000 kcal of energy intake.

Results

In this cohort, 58.3%±11.6 of total energy intake was derived from ultraprocessed (NOVA 4) foods. Ultraprocessed food intake was negatively correlated with diet quality (r=-0.32, p<0.001), fibre (r=-0.20, p<0.001) and protein (r = -0.40, p<0.001) and positively correlated with fat (r=0.18, p<0.001), saturated fat (r=0.14, p<0.001) and nmes (r=0.10, p<0.001) intake. Multivariable analysis suggests a positive association between ultraprocessed food (NOVA 4) consumption and CMR. However, this main effect was no longer observed after adjustment for diet quality (p=0.209). Findings from mediation analysis indicate that the effect of ultraprocessed food (NOVA 4) intake on CMR is mediated by diet quality (p<0.001).

Conclusions

Ultraprocessed food consumption is associated with a deterioration in diet quality and positively associated with CMR, although this association is mediated by and dependent on the quality of the diet. The negative impact of ultraprocessed food consumption on diet quality needs to be addressed and controlled studies are needed to fully comprehend whether the relationship between ultraprocessed food consumption and health is independent to its relationship with poor diet quality.",,doi:https://doi.org/10.1136/bmjnph-2020-000225; html:https://europepmc.org/articles/PMC8258022; pdf:https://europepmc.org/articles/PMC8258022?pdf=render 34828364,https://doi.org/10.3390/genes12111758,The Influence of CYP2D6 and CYP2C19 Genetic Variation on Diabetes Mellitus Risk in People Taking Antidepressants and Antipsychotics.,"Austin-Zimmerman I, Wronska M, Wang B, Irizar H, Thygesen JH, Bhat A, Denaxas S, Fatemifar G, Finan C, Harju-Seppänen J, Giannakopoulou O, Kuchenbaecker K, Zartaloudi E, McQuillin A, Bramon E.",,Genes,2021,2021-11-03,Y,Diabetes; CYP2C19; CYP2D6; Pharmacogenetics; Hba1c; Personalized Medicine; Uk Biobank,,,"CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with risk of diabetes. We examined whether individual genetic differences in CYP2D6 and CYP2C19 contribute to these effects. We identified 31,579 individuals taking antidepressants and 2699 taking antipsychotics within UK Biobank. Participants were classified as poor, intermediate, or normal metabolizers of CYP2D6, and as poor, intermediate, normal, rapid, or ultra-rapid metabolizers of CYP2C19. Risk of diabetes mellitus represented by HbA1c level was examined in relation to the metabolic phenotypes. CYP2D6 poor metabolizers taking paroxetine had higher Hb1Ac than normal metabolizers (mean difference: 2.29 mmol/mol; p < 0.001). Among participants with diabetes who were taking venlafaxine, CYP2D6 poor metabolizers had higher HbA1c levels compared to normal metabolizers (mean differences: 10.15 mmol/mol; p < 0.001. Among participants with diabetes who were taking fluoxetine, CYP2D6 intermediate metabolizers and decreased HbA1c, compared to normal metabolizers (mean difference -7.74 mmol/mol; p = 0.017). We did not observe any relationship between CYP2D6 or CYP2C19 metabolic status and HbA1c levels in participants taking antipsychotic medication. Our results indicate that the impact of genetic variation in CYP2D6 differs depending on diabetes status. Although our findings support existing clinical guidelines, further research is essential to inform pharmacogenetic testing for people taking antidepressants and antipsychotics.",,doi:https://doi.org/10.3390/genes12111758; html:https://europepmc.org/articles/PMC8620997; pdf:https://europepmc.org/articles/PMC8620997?pdf=render -37080566,https://doi.org/10.1183/13993003.01720-2022,Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.,"Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Moisés J, Peché R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",,The European respiratory journal,2023,2023-05-18,Y,,,,"

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render 34071236,https://doi.org/10.3390/ijms22115763,"Integration of the Microbiome, Metabolome and Transcriptomics Data Identified Novel Metabolic Pathway Regulation in Colorectal Cancer. ","Bisht V, Nash K, Xu Y, Agarwal P, Bosch S, Gkoutos GV, Acharjee A.",,International journal of molecular sciences,2021,2021-05-28,Y,,,,"Integrative multiomics data analysis provides a unique opportunity for the mechanistic understanding of colorectal cancer (CRC) in addition to the identification of potential novel therapeutic targets. In this study, we used public omics data sets to investigate potential associations between microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing datasets. We identified multiple potential interactions, for example 5-aminovalerate interacting with Adlercreutzia; cholesteryl ester interacting with bacterial genera Staphylococcus, Blautia and Roseburia. Using public single cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the ACAT1 gene that indirectly regulates the esterification of cholesterol. These findings demonstrate that the integration of multiomics data sets from diverse populations can help us in untangling the colorectal cancer pathogenesis as well as postulate the disease pathology mechanisms and therapeutic targets.",,doi:https://doi.org/10.3390/ijms22115763; html:https://europepmc.org/articles/PMC8198673; pdf:https://europepmc.org/articles/PMC8198673?pdf=render +37080566,https://doi.org/10.1183/13993003.01720-2022,Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.,"Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Moisés J, Peché R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",,The European respiratory journal,2023,2023-05-18,Y,,,,"

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render 36680646,https://doi.org/10.1007/s10654-022-00962-6,Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.,"Bowyer RCE, Huggins C, Toms R, Shaw RJ, Hou B, Thompson EJ, Kwong ASF, Williams DM, Kibble M, Ploubidis GB, Timpson NJ, Sterne JAC, Chaturvedi N, Steves CJ, Tilling K, Silverwood RJ, CONVALESCENCE Study.",,European journal of epidemiology,2023,2023-01-21,Y,Clustering; Longitudinal Studies; Symptom Patterns; Covid-19; Long Covid,,,"Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.",,doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf 33472926,https://doi.org/10.1212/wnl.0000000000011463,"Incidence, Prevalence and Healthcare Outcomes in Idiopathic Intracranial Hypertension: A Population Study. ","Miah L, Strafford H, Fonferko-Shadrach B, Hollinghurst J, Sawhney IM, Hadjikoutis S, Rees MI, Powell R, Lacey A, Pickrell WO.",,Neurology,2021,2021-01-20,Y,,,,"To characterise trends in incidence, prevalence, and healthcare outcomes in the idiopathic intracranial hypertension (IIH) population in Wales using routinely collected healthcare data. We used and validated primary and secondary care IIH diagnosis codes within the Secure Anonymised Information Linkage databank, to ascertain IIH cases and controls, in a retrospective cohort study between 2003 and 2017. We recorded body mass index (BMI), deprivation quintile, CSF diversion surgery and unscheduled hospital admissions in case and control cohorts. We analysed 35 million patient years of data. There were 1765 cases of IIH in 2017 (85% female). The prevalence and incidence of IIH in 2017 was 76/100,000 and 7.8/100,000/year, a significant increase from 2003 (corresponding figures=12/100,000 and 2.3/100,000/year) (p<0.001). IIH prevalence is associated with increasing BMI and increasing deprivation. The odds ratio for developing IIH in the least deprived quintile compared to the most deprived quintile, adjusted for gender and BMI, was 0.65 (95% CI 0.55 to 0.76). 9% of IIH cases had CSF shunts with less than 0.2% having bariatric surgery. Unscheduled hospital admissions were higher in the IIH cohort compared to controls (rate ratio=5.28, p<0.001) and in individuals with IIH and CSF shunts compared to those without shunts (rate ratio=2.02, p<0.01). IIH incidence and prevalence is increasing considerably, corresponding to population increases in BMI, and is associated with increased deprivation. This has important implications for healthcare professionals and policy makers given the comorbidities, complications and increased healthcare utilization associated with IIH.",,doi:https://doi.org/10.1212/WNL.0000000000011463; html:https://europepmc.org/articles/PMC8055349; pdf:https://europepmc.org/articles/PMC8055349?pdf=render 29992526,https://doi.org/10.1007/s11906-018-0877-8,An Overview of Metabolic Phenotyping in Blood Pressure Research.,"Tzoulaki I, Iliou A, Mikros E, Elliott P.",,Current hypertension reports,2018,2018-07-10,Y,Hypertension; Blood pressure; Metabolomics; Microbiome; Epidemiological Studies; Metabolic Phenotyping,,,"

Purpose of the review

This review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.

Recent findings

A variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation. Metabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.",,doi:https://doi.org/10.1007/s11906-018-0877-8; html:https://europepmc.org/articles/PMC6061189; pdf:https://europepmc.org/articles/PMC6061189?pdf=render PMC9645061,https://doi.org/,Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.,"Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",,International journal of population data science,,2022-11-25,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render -36753492,https://doi.org/10.1371/journal.pone.0281466,Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.,"Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.",,PloS one,2023,2023-02-08,Y,,,,"

Background

Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.

Methods

We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.

Results

In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.

Conclusions

Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.",,doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable 35845286,https://doi.org/10.1002/jha2.182,"An open-source, expert-designed decision tree application to support accurate diagnosis of myeloid malignancies.","Coats T, Bean D, Vatopoulou T, Vijayavalli D, El-Bashir R, Panopoulou A, Wood H, Wimalachandra M, Coppell J, Medd P, Furtado M, Tucker D, Kulasakeraraj A, Pawade J, Dobson R, Ireland R.",,EJHaem,2021,2021-03-26,Y,Myeloid Leukaemia; Classifications; Diagnostic Haematology; Clinical Haematology,,,"Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.",,doi:https://doi.org/10.1002/jha2.182; html:https://europepmc.org/articles/PMC9175663; pdf:https://europepmc.org/articles/PMC9175663?pdf=render +36753492,https://doi.org/10.1371/journal.pone.0281466,Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.,"Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.",,PloS one,2023,2023-02-08,Y,,,,"

Background

Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.

Methods

We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.

Results

In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.

Conclusions

Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.",,doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable 36329425,https://doi.org/10.1186/s12890-022-02189-3,Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps.,"Tibble H, Sheikh A, Tsanas A.",,BMC pulmonary medicine,2022,2022-11-03,Y,Asthma; Pharmacotherapy; Severity; Pharmacoepidemiology; Electronic Health Records; Treatment Guidelines,,,"

Background

Asthma severity is typically assessed through a retrospective assessment of the treatment required to control symptoms and to prevent exacerbations. The joint British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidelines encourage a stepwise approach to pharmacotherapy, and as such, current treatment step can be considered as a severity categorisation proxy. Briefly, the steps for adults can be summarised as: no controller therapy (Step 0), low-strength Inhaled Corticosteroids (ICS; Step 1), ICS plus Long-Acting Beta-2 Agonist (LABA; Step 2), medium-dose ICS + LABA (Step 3), and finally either an increase in strength or additional therapies (Step 4). This study aimed to investigate how BTS/SIGN Steps can be estimated from across a large cohort using electronic prescription records, and to describe the incidence of each BTS/SIGN Step in a general population.

Methods

There were 41,433,707 prescriptions, for 671,304 individuals, in the Asthma Learning Health System Scottish cohort, between 1/2009 and 3/2017. Days on which an individual had a prescription for at least one asthma controller (preventer) medication were labelled prescription events. A rule-based algorithm was developed for extracting the strength and volume of medication instructed to be taken daily from free-text data fields. Asthma treatment regimens were categorised by the combination of medications prescribed in the 120 days preceding any prescription event and categorised into BTS/SIGN treatment steps.

Results

Almost 4.5 million ALHS prescriptions were for asthma controllers. 26% of prescription events had no inhaled corticosteroid prescriptions in the preceding 120 days (Step 0), 16% were assigned to BTS/SIGN Step 1, 7% to Step 2, 21% to Step 3, and 30% to Step 4. The median days spent on a treatment step before a step-down in treatment was 297 days, whereas a step-up only took a median of 134 days.

Conclusion

We developed a reproducible methodology enabling researchers to estimate BTS/SIGN asthma treatment steps in population health studies, providing valuable insights into population and patient-specific trajectories, towards improving the management of asthma.",,doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render -36073628,https://doi.org/10.1161/jaha.122.026432,Differential Patterns and Outcomes of 20.6 Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.,"Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, Sharma G, Bullock-Palmer RP, Petersen SE, Mehta LS, Ullah W, Roguin A, Sun LY, Mamas MA.",,Journal of the American Heart Association,2022,2022-09-08,Y,Men; Essential hypertension; Atrial fibrillation; Stroke; Women; Sex characteristics; United States,,,"Background We describe sex-differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.",,doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?pdf=render 35836669,https://doi.org/10.1097/txd.0000000000001188,HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.,"Phagura N, Hussain A, Culliford A, Hodson J, Evison F, Gallier S, Borrows R, Lane HA, Briggs D, Sharif A.",,Transplantation direct,2021,2021-07-23,Y,,,,"The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods

In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results

PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001).

Conclusion

Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.",,doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render +36073628,https://doi.org/10.1161/jaha.122.026432,Differential Patterns and Outcomes of 20.6 Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.,"Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, Sharma G, Bullock-Palmer RP, Petersen SE, Mehta LS, Ullah W, Roguin A, Sun LY, Mamas MA.",,Journal of the American Heart Association,2022,2022-09-08,Y,Men; Essential hypertension; Atrial fibrillation; Stroke; Women; Sex characteristics; United States,,,"Background We describe sex-differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.",,doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?pdf=render 35531432,https://doi.org/10.1016/s2666-7568(22)00093-9,"Outcomes of SARS-CoV-2 omicron infection in residents of long-term care facilities in England (VIVALDI): a prospective, cohort study.","Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, COVID-19 Genomics UK consortium.",,The lancet. Healthy longevity,2022,2022-05-04,Y,,,,"

Background

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

Methods

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

Results

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

Interpretation

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

Funding

UK Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(22)00093-9; html:https://europepmc.org/articles/PMC9067940; pdf:https://europepmc.org/articles/PMC9067940?pdf=render 37053113,https://doi.org/10.1097/bot.0000000000002612,The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management.,"Cosic F, Kirzner N, Edwards E, Page R, Kimmel L, Gabbe B.",,Journal of orthopaedic trauma,2023,2023-09-01,N,,,,"

Objectives

To report on the long-term outcomes of the management of translated proximal humerus fractures.

Design

A prospective cohort study was conducted from January 2010 to December 2018.

Setting

Academic Level 1 trauma center.

Participants/patients

A total of 108 patients with a proximal humerus fracture with ≥100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.

Intervention

Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.

Main outcome measures

Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.

Results

Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (±20.2) years and in the nonoperative group was 73.3 (±15.3) years ( P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [±9.5] operative versus mean 41.3 [±8.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04-0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2-33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09-0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04-0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02-0.32; P = 0.001).

Conclusion

Translated proximal humerus fractures with ≥100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.

Level of evidence

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.",,doi:https://doi.org/10.1097/BOT.0000000000002612 30928998,https://doi.org/10.4193/rhin18.237,Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.,"Williamson E, Denaxas S, Morris S, Clarke CS, Thomas M, Evans H, Direk K, Gonzalez-Izquierdo A, Little P, Lund V, Blackshaw H, Schilder A, Philpott C, Hopkins C, Carpenter J, Programme Team OBOTM.",,Rhinology,2019,2019-08-01,N,,,,"

Background

Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use.

Methodology

Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia.

Results

Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular.

Conclusions

Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.",,doi:https://doi.org/10.4193/Rhin18.237 33020224,https://doi.org/10.1136/heartjnl-2020-317870,Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.,"Ball S, Banerjee A, Berry C, Boyle JR, Bray B, Bradlow W, Chaudhry A, Crawley R, Danesh J, Denniston A, Falter F, Figueroa JD, Hall C, Hemingway H, Jefferson E, Johnson T, King G, Lee KK, McKean P, Mason S, Mills NL, Pearson E, Pirmohamed M, Poon MTC, Priedon R, Shah A, Sofat R, Sterne JAC, Strachan FE, Sudlow CLM, Szarka Z, Whiteley W, Wyatt M, CVD-COVID-UK Consortium.",,Heart (British Cardiac Society),2020,2020-10-05,Y,epidemiology; Heart Disease; Health Care Delivery; Global Health Care Delivery; Aortic And Arterial Disease,,,"

Objective

To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects.

Methods

Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.

Results

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

Conclusions

Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.",,doi:https://doi.org/10.1136/heartjnl-2020-317870; html:https://europepmc.org/articles/PMC7536637; pdf:https://europepmc.org/articles/PMC7536637?pdf=render; pdf:https://heart.bmj.com/content/heartjnl/106/24/1890.full.pdf 36609412,https://doi.org/10.1136/archdischild-2022-324713,"Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.","Goulding A, McQuaid F, Lindsay L, Agrawal U, Auyeung B, Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft L, Hopkins L, McCowan C, McLaughlin T, Moore E, Ritchie L, Simpson CR, Taylor B, Fenton L, Pollock L, Gale C, Kurinczuk JJ, Robertson C, Sheikh A, Stock S, Wood R.",,Archives of disease in childhood. Fetal and neonatal edition,2023,2023-01-06,Y,epidemiology; Neonatology; Covid-19,,,"

Objectives

To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections.

Design

Population-based cohort study.

Setting and population

All live births in Scotland, 1 March 2020-31 January 2022.

Results

There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection.

Implications and relevance

Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.",,doi:https://doi.org/10.1136/archdischild-2022-324713; html:https://europepmc.org/articles/PMC10313998; pdf:https://europepmc.org/articles/PMC10313998?pdf=render -36384749,https://doi.org/10.1136/heartjnl-2022-321733,Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.,"Raisi-Estabragh Z, Cooper J, Bethell MS, McCracken C, Lewandowski AJ, Leeson P, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2023,2023-03-10,Y,epidemiology; Magnetic Resonance Imaging; risk factors,,,"

Objective

To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.

Methods

Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.

Results

258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).

Conclusions

Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.",,doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render 35443953,https://doi.org/10.1136/bmjopen-2021-056523,Can we accurately forecast non-elective bed occupancy and admissions in the NHS? A time-series MSARIMA analysis of longitudinal data from an NHS Trust.,"Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",,BMJ open,2022,2022-04-20,Y,epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine,,,"

Objectives

The main objective of the study was to develop more accurate and precise short-term forecasting models for admissions and bed occupancy for an NHS Trust located in Bristol, England. Subforecasts for the medical and surgical specialties, and for different lengths of stay were realised DESIGN: Autoregressive integrated moving average models were specified on a training dataset of daily count data, then tested on a 6-week forecast horizon. Explanatory variables were included in the models: day of the week, holiday days, lagged temperature and precipitation.

Setting

A secondary care hospital in an NHS Trust in South West England.

Participants

Hospital admissions between September 2016 and March 2020, comprising 1291 days.

Primary and secondary outcome measures

The accuracy of the forecasts was assessed through standard measures, as well as compared with the actual data using accuracy thresholds of 10% and 20% of the mean number of admissions or occupied beds.

Results

The overall Autoregressive Integrated Moving Average (ARIMA) admissions forecast was compared with the Trust's forecast, and found to be more accurate, namely, being closer to the actual value 95.6% of the time. Furthermore, it was more precise than the Trust's. The subforecasts, as well as those for bed occupancy, tended to be less accurate compared with the overall forecasts. All of the explanatory variables improved the forecasts.

Conclusions

ARIMA models can forecast non-elective admissions in an NHS Trust accurately on a 6-week horizon, which is an improvement on the current predictive modelling in the Trust. These models can be readily applied to other contexts, improving patient flow.",,doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render +36384749,https://doi.org/10.1136/heartjnl-2022-321733,Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.,"Raisi-Estabragh Z, Cooper J, Bethell MS, McCracken C, Lewandowski AJ, Leeson P, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2023,2023-03-10,Y,epidemiology; Magnetic Resonance Imaging; risk factors,,,"

Objective

To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.

Methods

Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.

Results

258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).

Conclusions

Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.",,doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render 33185672,https://doi.org/10.1093/jamia/ocaa295,Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2.,"Wu H, Zhang H, Karwath A, Ibrahim Z, Shi T, Zhang X, Wang K, Sun J, Dhaliwal K, Bean D, Cardoso VR, Li K, Teo JT, Banerjee A, Gao-Smith F, Whitehouse T, Veenith T, Gkoutos GV, Wu X, Dobson R, Guthrie B.",,Journal of the American Medical Informatics Association : JAMIA,2021,2021-03-01,Y,Decision Support; Risk Prediction; Ensemble Learning; Covid-19; Model Synergy,,,"

Objective

Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning.

Materials and methods

In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness.

Results

Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts.

Discussion

When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.

Conclusions

Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients.",,doi:https://doi.org/10.1093/jamia/ocaa295; html:https://europepmc.org/articles/PMC7717299; pdf:https://europepmc.org/articles/PMC7717299?pdf=render 33845909,https://doi.org/10.1186/s13326-021-00241-5,Improved characterisation of clinical text through ontology-based vocabulary expansion.,"Slater LT, Bradlow W, Ball S, Hoehndorf R, Gkoutos GV.",,Journal of biomedical semantics,2021,2021-04-12,Y,Ontology; Text Mining; Semantic Similarity; Vocabulary Expansion,,,"

Background

Biomedical ontologies contain a wealth of metadata that constitutes a fundamental infrastructural resource for text mining. For several reasons, redundancies exist in the ontology ecosystem, which lead to the same entities being described by several concepts in the same or similar contexts across several ontologies. While these concepts describe the same entities, they contain different sets of complementary metadata. Linking these definitions to make use of their combined metadata could lead to improved performance in ontology-based information retrieval, extraction, and analysis tasks.

Results

We develop and present an algorithm that expands the set of labels associated with an ontology class using a combination of strict lexical matching and cross-ontology reasoner-enabled equivalency queries. Across all disease terms in the Disease Ontology, the approach found 51,362 additional labels, more than tripling the number defined by the ontology itself. Manual validation by a clinical expert on a random sampling of expanded synonyms over the Human Phenotype Ontology yielded a precision of 0.912. Furthermore, we found that annotating patient visits in MIMIC-III with an extended set of Disease Ontology labels led to semantic similarity score derived from those labels being a significantly better predictor of matching first diagnosis, with a mean average precision of 0.88 for the unexpanded set of annotations, and 0.913 for the expanded set.

Conclusions

Inter-ontology synonym expansion can lead to a vast increase in the scale of vocabulary available for text mining applications. While the accuracy of the extended vocabulary is not perfect, it nevertheless led to a significantly improved ontology-based characterisation of patients from text in one setting. Furthermore, where run-on error is not acceptable, the technique can be used to provide candidate synonyms which can be checked by a domain expert.",,doi:https://doi.org/10.1186/s13326-021-00241-5; html:https://europepmc.org/articles/PMC8042947; pdf:https://europepmc.org/articles/PMC8042947?pdf=render 35305568,https://doi.org/10.1186/s12882-022-02742-6,Interaction between socioeconomic deprivation and ethnicity for likelihood of receiving living-donor kidney transplantation.,"Khalil K, Brotherton A, Moore S, Evison F, Gallier S, Hodson J, Sharif A.",,BMC nephrology,2022,2022-03-19,Y,Diversity; Kidney transplantation; Ethnicity; Deprivation; Living Kidney Donors,,,"

Background

The interplay between ethnicity and socioeconomic deprivation for living-donor kidney transplantation (LDKT) opportunities is unclear.

Methods

Data for 2040 consecutive kidney-alone transplant recipients receiving an allograft between 1st January 2007 and 30th June 2020 at a single center were retrospectively analyzed. The associations between the proportions of transplants that were LDKT (versus deceased donation) and both ethnicity and socioeconomic deprivation were assessed, with the latter quantified by the Index of Multiple Deprivation (IMD) quintile.

Results

The cohort comprised recipients of White (64.7%), South Asian (21.7%), Black (7.0%) and other (6.6%) ethnic groups. Recipients tended to be from socioeconomically deprived areas, with the most deprived quintile being the most frequently observed (quintile 1: 38.6% of patients); non-White recipients were significantly more likely to live in socioeconomically deprived areas (p < 0.001). Overall, 36.5% of transplants were LDKT, with this proportion declining progressively with socioeconomic deprivation, from 50.4 to 27.6% in the least versus most deprived IMD quintile (p < 0.001). A significant difference across recipient ethnicities was also observed, with the proportion of LDKTs ranging from 43.2% in White recipients to 17.8% in Black recipients (p < 0.001). Both socioeconomic deprivation (p < 0.001) and ethnicity (p = 0.005) remained significant predictors of LDKT on multivariable analysis, with a significant interaction between these factors also being observed (p < 0.001). Further assessment of this interaction effect found that, whilst there was a marked difference in the proportions of transplants that were LDKT between White versus non-White recipients in the most socioeconomically deprived groups (39.5% versus 19.3%), no such difference was seen in the least deprived recipients (48.5% versus 51.9%).

Conclusions

Whilst both socioeconomic deprivation and non-White ethnicity are independent predictors for lower proportions of LDKTs, the significant interaction between the two factors should be appreciated.",,doi:https://doi.org/10.1186/s12882-022-02742-6; html:https://europepmc.org/articles/PMC8934457; pdf:https://europepmc.org/articles/PMC8934457?pdf=render @@ -514,12 +515,12 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 32614817,https://doi.org/10.1371/journal.pcbi.1008031,Estimation of country-level basic reproductive ratios for novel Coronavirus (SARS-CoV-2/COVID-19) using synthetic contact matrices.,"Hilton J, Keeling MJ.",,PLoS computational biology,2020,2020-07-02,Y,,,,"The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.",,doi:https://doi.org/10.1371/journal.pcbi.1008031; html:https://europepmc.org/articles/PMC7363110; pdf:https://europepmc.org/articles/PMC7363110?pdf=render 35835543,https://doi.org/10.1136/heartjnl-2022-321196,Eligibility for early rhythm control in patients with atrial fibrillation in the UK Biobank.,"Kany S, Cardoso VR, Bravo L, Williams JA, Schnabel R, Fabritz L, Gkoutos GV, Kirchhof P.",,Heart (British Cardiac Society),2022,2022-11-10,Y,Atrial fibrillation; Stroke; Catheter ablation,,,"

Objective

The Early Treatment of Atrial Fibrillation for Stroke Prevention (EAST-AFNET4) trial showed a clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF). The generalisability of the results in the general population is not known.

Methods

Participants in the population-based UK Biobank were assessed for eligibility based on the EAST-AFNET4 inclusion/exclusion criteria. Treatment of all eligible participants was classified as early rhythm-control (antiarrhythmic drug therapy or AF ablation) or usual care. To assess treatment effects, primary care data and Hospital Episode Statistics were merged with UK Biobank data.Efficacy and safety outcomes were compared between groups in the entire cohort and in a propensity-matched data set.

Results

AF was present in 35 526/502 493 (7.1%) participants, including 8340 (988 with AF <1 year) with AF at enrolment and 27 186 with incident AF during follow-up. Most participants (22 003/27 186; 80.9%) with incident AF were eligible for early rhythm-control.Eligible participants were older (70 years vs 63 years) and more likely to be female (42% vs 21%) compared with ineligible patients. Of 9004 participants with full primary care data, 874 (9.02%) received early rhythm-control. Safety outcomes were not different between patients receiving early rhythm-control and controls. The primary outcome of EAST-AFNET 4, a composite of cardiovascular death, stroke/transient ischaemic attack and hospitalisation for heart failure or acute coronary syndrome occurred less often in participants receiving early rhythm-control compared with controls in the entire cohort (HR 0.82, 95% CI 0.71 to 0.94, p=0.005). In the propensity-score matched analysis, early rhythm-control did not significantly decrease of the primary outcome compared with usual care (HR 0.87, 95% CI 0.72 to 1.04, p=0.124).

Conclusion

Around 80% of participants diagnosed with AF in the UK population are eligible for early rhythm-control. Early rhythm-control therapy was safe in routine care.",,doi:https://doi.org/10.1136/heartjnl-2022-321196; html:https://europepmc.org/articles/PMC9664114; pdf:https://europepmc.org/articles/PMC9664114?pdf=render 33728401,https://doi.org/10.1038/s42254-020-0178-4,Modelling COVID-19.,"Vespignani A, Tian H, Dye C, Lloyd-Smith JO, Eggo RM, Shrestha M, Scarpino SV, Gutierrez B, Kraemer MUG, Wu J, Leung K, Leung GM.",,Nature reviews. Physics,2020,2020-05-06,Y,Applied Mathematics; Complex Networks,,,"As the COVID-19 pandemic continues, mathematical epidemiologists share their views on what models reveal about how the disease has spread, the current state of play and what work still needs to be done.",Vespignani et al. used mathematical models to model the epidemic of covid-19 and to predict future scenarios for possible interventions and inform policy and practice.,doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render +35814295,https://doi.org/10.1038/s43856-022-00146-z,Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.,"Wong NCK, Meshkinfamfard S, Turbé V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka RJ, Cooke GS, McKendry RA, Atchison CJ, Bharath AA.",,Communications medicine,2022,2022-07-06,Y,Databases; Public Health,,,"

Background

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.

Methods

Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.

Results

Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).

Conclusions

Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.",,doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render 36921925,https://doi.org/10.1136/bmj-2022-072808,Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.,"Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hernán MA, Sterne JAC.",,BMJ (Clinical research ed.),2023,2023-03-15,Y,,,,"

Objective

To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.

Design

Matched cohort study, emulating a comparative effectiveness trial.

Setting

Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.

Participants

3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.

Intervention

Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.

Main outcome measures

Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.

Results

1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.

Conclusions

This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",,doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render 36446790,https://doi.org/10.1038/s41467-022-35017-7,Genetically personalised organ-specific metabolic models in health and disease.,"Foguet C, Xu Y, Ritchie SC, Lambert SA, Persyn E, Nath AP, Davenport EE, Roberts DJ, Paul DS, Di Angelantonio E, Danesh J, Butterworth AS, Yau C, Inouye M.",,Nature communications,2022,2022-11-29,Y,,,,"Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage human genome-scale metabolic networks to define how genetic variants affect biochemical reaction fluxes across major human tissues, including skeletal muscle, adipose, liver, brain and heart. As proof of concept, we build personalised organ-specific metabolic flux models for 524,615 individuals of the INTERVAL and UK Biobank cohorts and perform a fluxome-wide association study (FWAS) to identify 4312 associations between personalised flux values and the concentration of metabolites in blood. Furthermore, we apply FWAS to identify 92 metabolic fluxes associated with the risk of developing coronary artery disease, many of which are linked to processes previously described to play in role in the disease. Our work demonstrates that genetically personalised metabolic models can elucidate the downstream effects of genetic variants on biochemical reactions involved in common human diseases.",,doi:https://doi.org/10.1038/s41467-022-35017-7; html:https://europepmc.org/articles/PMC9708841; pdf:https://europepmc.org/articles/PMC9708841?pdf=render -35814295,https://doi.org/10.1038/s43856-022-00146-z,Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.,"Wong NCK, Meshkinfamfard S, Turbé V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka RJ, Cooke GS, McKendry RA, Atchison CJ, Bharath AA.",,Communications medicine,2022,2022-07-06,Y,Databases; Public Health,,,"

Background

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.

Methods

Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.

Results

Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).

Conclusions

Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.",,doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render 36541282,https://doi.org/10.14814/phy2.15546,Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.,"Gheorghita M, Wikner M, Cawthorn A, Oyelade T, Nemeth K, Rockenschaub P, Gonzalez Hernandez F, Swanepoel N, Lilaonitkul W, Mani AR.",,Physiological reports,2022,2022-12-01,Y,Variability; Survival; Sepsis; Entropy; Oxygen saturation; Spo2,,,"Recent studies have found that oxygen saturation (SpO2 ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30 min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p < 0.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2 , and ventilation status. When SpO2 entropy was combined with mean SpO2 , the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.",,doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render -37561116,https://doi.org/10.7554/elife.85332,Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP.,"Lemanska A, Andrews C, Fisher L, Bacon S, Frampton AE, Mehrkar A, Inglesby P, Davy S, Roberts K, Patalay P, Goldacre B, MacKenna B, OpenSAFELY Collaborative, Walker AJ.",,eLife,2023,2023-08-10,Y,Human; Pancreatic cancer; epidemiology; Global Health; Healthcare; Healthcare Crisis; Covid-19; Healthcare Disruption,,,"

Background

Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic.

Methods

With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates.

Results

The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (±11 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital admissions, and deaths were not affected.

Conclusions

The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.

Funding

This work was jointly funded by the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). This work was funded by Medical Research Council (MRC) grant reference MR/W021390/1 as part of the postdoctoral fellowship awarded to AL and undertaken at the Bennett Institute, University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UKHSA), or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.",,doi:https://doi.org/10.7554/eLife.85332; html:https://europepmc.org/articles/PMC10414967; pdf:https://europepmc.org/articles/PMC10414967?pdf=render 33632765,https://doi.org/10.1136/thoraxjnl-2020-215986,"Neutrophils in asthma: the good, the bad and the bacteria.","Crisford H, Sapey E, Rogers GB, Taylor S, Nagakumar P, Lokwani R, Simpson JL.",,Thorax,2021,2021-02-25,Y,Asthma; Bacterial Infection; Paediatric Asthma; Asthma Mechanisms; Neutrophil Biology,,,"Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.",,doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render +37561116,https://doi.org/10.7554/elife.85332,Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP.,"Lemanska A, Andrews C, Fisher L, Bacon S, Frampton AE, Mehrkar A, Inglesby P, Davy S, Roberts K, Patalay P, Goldacre B, MacKenna B, OpenSAFELY Collaborative, Walker AJ.",,eLife,2023,2023-08-10,Y,Human; Pancreatic cancer; epidemiology; Global Health; Healthcare; Healthcare Crisis; Covid-19; Healthcare Disruption,,,"

Background

Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic.

Methods

With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates.

Results

The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (±11 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital admissions, and deaths were not affected.

Conclusions

The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.

Funding

This work was jointly funded by the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). This work was funded by Medical Research Council (MRC) grant reference MR/W021390/1 as part of the postdoctoral fellowship awarded to AL and undertaken at the Bennett Institute, University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UKHSA), or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.",,doi:https://doi.org/10.7554/eLife.85332; html:https://europepmc.org/articles/PMC10414967; pdf:https://europepmc.org/articles/PMC10414967?pdf=render 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"

Objectives

To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.

Design

An EHR-based, retrospective cohort study.

Setting

Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).

Participants

In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.

Main outcome measures

One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.

Results

From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.

Conclusions

We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897; pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897 33371011,https://doi.org/10.1136/bmjresp-2020-000770,Physiological tests of small airways function in diagnosing asthma: a systematic review. ,"Almeshari MA, Alobaidi NY, Edgar RG, Stockley J, Sapey E.",,BMJ open respiratory research,2020,2020-12-01,Y,,,,"Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed to assess whether the most commonly reported tests of small airways function could contribute to the diagnosis of asthma. Standard systematic review methodology was used, and a range of electronic databases was searched (Embase, MEDLINE, CINAHL, CENTRAL, Web of Science, DARE). Studies that included physiological tests of small airways function to diagnose asthma in adults were included, with no restrictions on language or date. The risk of bias and quality assessment tools used were Agency for Healthcare Research and Quality tool for cross-sectional studies and Quality Assessment of Diagnostic Accuracy Studies 2 for diagnostic test accuracy (DTA) studies. 7072 studies were identified and 10 studies met review criteria. 7 included oscillation techniques and 5 included maximal mid-expiratory flow (MMEF). Studies were small and of variable quality. In oscillometry, total resistance (R5) and reactance at 5 Hz (X5) was altered in asthma compared with healthy controls. The percentage predicted of MMEF was lower in patients with asthma compared with controls in all studies and lower than the % predicted forced expiratory volume in 1 s. In DTA of oscillometry, R5 showed a sensitivity between 69% and 72% and specificity between 61% and 86%. There were differences in the results of physiological tests of small airway function in patients with asthma compared with controls. However, studies are small and heterogeneous. Further studies are needed to assess the effectiveness of these tests on a larger scale, including studies to determine which test methodology is the most useful in asthma.",,doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?pdf=render 31789939,https://doi.org/10.1097/ede.0000000000001113,Could Greater Physical Activity Reduce Population Prevalence and Socioeconomic Inequalities in Children's Mental Health Problems? A Policy Simulation.,"Chigogora S, Pearce A, Law C, Viner R, Chittleborough C, Griffiths LJ, Hope S.",,"Epidemiology (Cambridge, Mass.)",2020,2020-01-01,Y,,,,"

Background

One in four children 5-16 years (y) of age shows signs of mental health problems in the United Kingdom; risk is higher in economically disadvantaged groups. Greater physical activity is associated with lower risk of internalizing problems such as depression and anxiety. We simulated the potential impact of population-wide physical activity interventions on overall prevalence of internalizing problems, and by family income. Interventions were based on the World Health Organization (WHO) children's target of 60 minutes (min) of moderate-to-vigorous physical activity per day and trial evidence.

Methods

Data were from the UK Millennium Cohort Study, a population-representative cohort of children born in 2000-2002. Household income (5 y) was the exposure; internalizing problems (outcome) were measured using the Strengths and Difficulties Questionnaire (11 y). Of 18,296 singletons, 6,497 had accelerometer physical activity data (mediator, manipulated to simulate interventions) at 7 y. We predicted probabilities of outcome according to exposure in marginal structural models, weighted for attrition and confounding, and adjusted for observed mediator. We then re-estimated probabilities in different physical activity intervention scenarios, assessing income inequalities in internalizing problems with risk ratios (RRs) and differences (RDs) according to income quintile.

Results

Simulating universal achievement of the WHO target led to little change in prevalence (10% [95% CI = 8%, 12%]) and socioeconomic inequalities in internalizing problems; RR: 2.2 (1.1, 3.4); RD: 8% [5%,13%]). More modest increases in physical activity achieved weaker results.

Conclusions

Our simulations suggest that large increases in moderate-to-vigorous physical activity in the United Kingdom would have little effect on prevalence and inequalities in child mental health problems.","This UK based prospective cohort study looked at the potential impact of physical activity on 'internalizing problems' such as depression in children. They measured physical activity level at 7 years, and looked whether mental health problems existed at 11 years, adjusting approrpiately for confounders (ethnicity, maternal age at birth, neighbourhood safety, childhood illness, etc). They conclude that a small reduction in mental health problems could be observed but not enough to justify the national policy of encouraging 60 min of mod-vigorous exercise a day for all children",doi:https://doi.org/10.1097/EDE.0000000000001113; html:https://europepmc.org/articles/PMC6889907; pdf:https://europepmc.org/articles/PMC6889907?pdf=render @@ -534,17 +535,17 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 36895179,https://doi.org/10.1093/eurjpc/zwad055,Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.,"Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.",,European journal of preventive cardiology,2023,2023-08-01,Y,Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records,,,"

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.",,doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render; pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf 34082702,https://doi.org/10.1186/s12874-021-01301-1,Incorporating single-arm studies in meta-analysis of randomised controlled trials: a simulation study.,"Singh J, Abrams KR, Bujkiewicz S.",,BMC medical research methodology,2021,2021-06-03,Y,Meta-analysis; Evidence Synthesis; Real World Data; Arm-Based Methods; Bayesian Hierarchical Methods; Single-Arm Studies,,,"

Background

Use of real world data (RWD) from non-randomised studies (e.g. single-arm studies) is increasingly being explored to overcome issues associated with data from randomised controlled trials (RCTs). We aimed to compare methods for pairwise meta-analysis of RCTs and single-arm studies using aggregate data, via a simulation study and application to an illustrative example.

Methods

We considered contrast-based methods proposed by Begg & Pilote (1991) and arm-based methods by Zhang et al (2019). We performed a simulation study with scenarios varying (i) the proportion of RCTs and single-arm studies in the synthesis (ii) the magnitude of bias, and (iii) between-study heterogeneity. We also applied methods to data from a published health technology assessment (HTA), including three RCTs and 11 single-arm studies.

Results

Our simulation study showed that the hierarchical power and commensurate prior methods by Zhang et al provided a consistent reduction in uncertainty, whilst maintaining over-coverage and small error in scenarios where there was limited RCT data, bias and differences in between-study heterogeneity between the two sets of data. The contrast-based methods provided a reduction in uncertainty, but performed worse in terms of coverage and error, unless there was no marked difference in heterogeneity between the two sets of data.

Conclusions

The hierarchical power and commensurate prior methods provide the most robust approach to synthesising aggregate data from RCTs and single-arm studies, balancing the need to account for bias and differences in between-study heterogeneity, whilst reducing uncertainty in estimates. This work was restricted to considering a pairwise meta-analysis using aggregate data.",,doi:https://doi.org/10.1186/s12874-021-01301-1; html:https://europepmc.org/articles/PMC8176581; pdf:https://europepmc.org/articles/PMC8176581?pdf=render 31774502,https://doi.org/10.1093/ehjcvp/pvz071,An observational study of international normalized ratio control according to NICE criteria in patients with non-valvular atrial fibrillation: the SAIL Warfarin Out of Range Descriptors Study (SWORDS).,"Harris DE, Thayer D, Wang T, Brooks C, Murley G, Gravenor M, Hill NR, Lister S, Halcox J.",,European heart journal. Cardiovascular pharmacotherapy,2021,2021-01-01,Y,Atrial fibrillation; Warfarin; Pharmacoepidemiology,Improving Public Health,,"

Aims

In patients with non-valvular atrial fibrillation prescribed warfarin, the UK National Institute of Health and Care Excellence (NICE) defines poor anticoagulation as a time in therapeutic range (TTR) of <65%, any two international normalized ratios (INRs) within a 6-month period of ≤1.5 ('low'), two INRs ≥5 within 6 months, or any INR ≥8 ('high'). Our objectives were to (i) quantify the number of patients with poor INR control and (ii) describe the demographic and clinical characteristics associated with poor INR control.

Method and results

Linked anonymized health record data for Wales, UK (2006-2017) was used to evaluate patients prescribed warfarin who had at least 6 months of INR data. 32 380 patients were included. In total, 13 913 (43.0%) patients had at least one of the NICE markers of poor INR control. Importantly, in the 24 123 (74.6%) of the cohort with an acceptable TTR (≥65%), 5676 (23.5%) had either low or high INR readings at some point in their history. In a multivariable regression female gender, age (≥75 years), excess alcohol, diabetes heart failure, ischaemic heart disease, and respiratory disease were independently associated with all markers of poor INR control.

Conclusion

Acceptable INR control according to NICE standards is poor. Of those with an acceptable TTR (>65%), one-quarter still had unacceptably low or high INR levels according to NICE criteria. Thus, only using TTR to assess effectiveness with warfarin has the potential to miss a large number of patients with non-therapeutic INRs who are likely to be at increased risk.","This retrospective observational cohort study aimed to quanitfy the number of patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin who exhibit NICE-defined poor international normalised ratio (INR) control. Another objective was to describe the relationship between demographic and clinical characteristics of these patients and poor INR control. The results from statistical analyses in this study suggest a considerable opportunity to improve both embloc and bleeding risk, eben though the relationship between poor INR control and these clinical outcomes remains to be determined.",doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?pdf=render -34894331,https://doi.org/10.1007/s10461-021-03551-y,Influence of Material Deprivation on Clinical Outcomes Among People Living with HIV in High-Income Countries: A Systematic Review and Meta-analysis.,"Papageorgiou V, Davies B, Cooper E, Singer A, Ward H.",,AIDS and behavior,2022,2021-12-11,Y,HIV; Meta-analysis; Systematic review; Antiretroviral therapy; Socioeconomic Factors; Viral Suppression; Social Determinants Of Health,,,"Despite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review to explore associations between social determinants and HIV treatment outcomes (viral suppression and treatment adherence) in high-income countries. A random effects meta-analysis was performed where there were consistent measurements of exposures. We identified 83 observational studies eligible for inclusion. Social determinants linked to material deprivation were identified as education, employment, food security, housing, income, poverty/deprivation, socioeconomic status/position, and social class; however, their measurement and definition varied across studies. Our review suggests a social gradient of health persists in the HIV care continuum; people living with HIV who reported material deprivation were less likely to be virologically suppressed or adherent to antiretrovirals. Future research should use an ecosocial approach to explore these interactions across the lifecourse to help propose a causal pathway.",,doi:https://doi.org/10.1007/s10461-021-03551-y; html:https://europepmc.org/articles/PMC9046343; pdf:https://europepmc.org/articles/PMC9046343?pdf=render 35879616,https://doi.org/10.1038/s41591-022-01909-w,Symptoms and risk factors for long COVID in non-hospitalized adults.,"Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.",,Nature medicine,2022,2022-07-25,Y,,,,"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.",,doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render; pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf -36933612,https://doi.org/10.1016/j.cct.2023.107162,Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.,"Macnair A, Nankivell M, Murray ML, Rosen SD, Appleyard S, Sydes MR, Forcat S, Welland A, Clarke NW, Mangar S, Kynaston H, Kockelbergh R, Al-Hasso A, Deighan J, Marshall J, Parmar M, Langley RE, Gilbert DC.",,Contemporary clinical trials,2023,2023-03-16,N,Cardiovascular disease; prostate cancer; Clinical Trials; Healthcare Systems Data,,,"

Background

Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources.

Methods

Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored.

Results

From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR.

Conclusion

Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD.",,doi:https://doi.org/10.1016/j.cct.2023.107162 +34894331,https://doi.org/10.1007/s10461-021-03551-y,Influence of Material Deprivation on Clinical Outcomes Among People Living with HIV in High-Income Countries: A Systematic Review and Meta-analysis.,"Papageorgiou V, Davies B, Cooper E, Singer A, Ward H.",,AIDS and behavior,2022,2021-12-11,Y,HIV; Meta-analysis; Systematic review; Antiretroviral therapy; Socioeconomic Factors; Viral Suppression; Social Determinants Of Health,,,"Despite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review to explore associations between social determinants and HIV treatment outcomes (viral suppression and treatment adherence) in high-income countries. A random effects meta-analysis was performed where there were consistent measurements of exposures. We identified 83 observational studies eligible for inclusion. Social determinants linked to material deprivation were identified as education, employment, food security, housing, income, poverty/deprivation, socioeconomic status/position, and social class; however, their measurement and definition varied across studies. Our review suggests a social gradient of health persists in the HIV care continuum; people living with HIV who reported material deprivation were less likely to be virologically suppressed or adherent to antiretrovirals. Future research should use an ecosocial approach to explore these interactions across the lifecourse to help propose a causal pathway.",,doi:https://doi.org/10.1007/s10461-021-03551-y; html:https://europepmc.org/articles/PMC9046343; pdf:https://europepmc.org/articles/PMC9046343?pdf=render 37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render +36933612,https://doi.org/10.1016/j.cct.2023.107162,Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.,"Macnair A, Nankivell M, Murray ML, Rosen SD, Appleyard S, Sydes MR, Forcat S, Welland A, Clarke NW, Mangar S, Kynaston H, Kockelbergh R, Al-Hasso A, Deighan J, Marshall J, Parmar M, Langley RE, Gilbert DC.",,Contemporary clinical trials,2023,2023-03-16,N,Cardiovascular disease; prostate cancer; Clinical Trials; Healthcare Systems Data,,,"

Background

Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources.

Methods

Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored.

Results

From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR.

Conclusion

Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD.",,doi:https://doi.org/10.1016/j.cct.2023.107162 35256633,https://doi.org/10.1038/s41598-022-07291-4,Shared genetic loci for body fat storage and adipocyte lipolysis in humans.,"Kulyté A, Lundbäck V, Arner P, Strawbridge RJ, Dahlman I.",,Scientific reports,2022,2022-03-07,Y,,,,"Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.",,doi:https://doi.org/10.1038/s41598-022-07291-4; html:https://europepmc.org/articles/PMC8901764; pdf:https://europepmc.org/articles/PMC8901764?pdf=render 37000839,https://doi.org/10.1371/journal.pone.0279076,Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.,"Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",,PloS one,2023,2023-03-31,Y,,,,"Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.",,doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render 34556677,https://doi.org/10.1038/s41598-021-96189-8,Combining multi-site magnetic resonance imaging with machine learning predicts survival in pediatric brain tumors.,"Grist JT, Withey S, Bennett C, Rose HEL, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Bailey S, Clifford SC, Mitra D, Arvanitis TN, Auer DP, Avula S, Grundy R, Peet AC.",,Scientific reports,2021,2021-09-23,Y,,,,"Brain tumors represent the highest cause of mortality in the pediatric oncological population. Diagnosis is commonly performed with magnetic resonance imaging. Survival biomarkers are challenging to identify due to the relatively low numbers of individual tumor types. 69 children with biopsy-confirmed brain tumors were recruited into this study. All participants had perfusion and diffusion weighted imaging performed at diagnosis. Imaging data were processed using conventional methods, and a Bayesian survival analysis performed. Unsupervised and supervised machine learning were performed with the survival features, to determine novel sub-groups related to survival. Sub-group analysis was undertaken to understand differences in imaging features. Survival analysis showed that a combination of diffusion and perfusion imaging were able to determine two novel sub-groups of brain tumors with different survival characteristics (p < 0.01), which were subsequently classified with high accuracy (98%) by a neural network. Analysis of high-grade tumors showed a marked difference in survival (p = 0.029) between the two clusters with high risk and low risk imaging features. This study has developed a novel model of survival for pediatric brain tumors. Tumor perfusion plays a key role in determining survival and should be considered as a high priority for future imaging protocols.",,doi:https://doi.org/10.1038/s41598-021-96189-8; html:https://europepmc.org/articles/PMC8460620; pdf:https://europepmc.org/articles/PMC8460620?pdf=render 37139857,https://doi.org/10.1111/dom.15102,Impact of severe hypoglycaemia requiring hospitalization on mortality in people with type 1 diabetes: A national retrospective observational cohort study.,"Moser O, Rafferty J, Eckstein ML, Aziz F, Bain SC, Bergenstal R, Sourij H, Thomas RL.",,"Diabetes, obesity & metabolism",2023,2023-05-04,N,Mortality; type 1 diabetes; Risk Prediction; Severe Hypoglycaemia,,,"

Aims

To assess if the risk of all-cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization.

Materials and methods

We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all-cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model.

Results

A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1-7.8) deaths/ 1000 person-years (crude) and 15.31 (13.3-17.63) deaths/ 1000 person-years (age-adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0-29.6; crude) and 53.8 (44.6-64.7) deaths/ 1000 person-years (age-adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1-34.0; crude) and 72.8 (59.2-89.5) deaths/ 1000 person-years (age-adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0-37.3; crude) and 86.3 (71.7-103.9) deaths/ 1000 person years (age-adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009-0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036-0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885-0.951]).

Conclusions

The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization.",,doi:https://doi.org/10.1111/dom.15102 37587484,https://doi.org/10.1186/s12874-023-02000-9,Implementation of the trial emulation approach in medical research: a scoping review.,"Scola G, Chis Ster A, Bean D, Pareek N, Emsley R, Landau S.",,BMC medical research methodology,2023,2023-08-16,N,Causal Inference; Observational Data; Target Trial; Trial Emulation,,,"

Background

When conducting randomised controlled trials is impractical, an alternative is to carry out an observational study. However, making valid causal inferences from observational data is challenging because of the risk of several statistical biases. In 2016 Hernán and Robins put forward the 'target trial framework' as a guide to best design and analyse observational studies whilst preventing the most common biases. This framework consists of (1) clearly defining a causal question about an intervention, (2) specifying the protocol of the hypothetical trial, and (3) explaining how the observational data will be used to emulate it.

Methods

The aim of this scoping review was to identify and review all explicit attempts of trial emulation studies across all medical fields. Embase, Medline and Web of Science were searched for trial emulation studies published in English from database inception to February 25, 2021. The following information was extracted from studies that were deemed eligible for review: the subject area, the type of observational data that they leveraged, and the statistical methods they used to address the following biases: (A) confounding bias, (B) immortal time bias, and (C) selection bias.

Results

The search resulted in 617 studies, 38 of which we deemed eligible for review. Of those 38 studies, most focused on cardiology, infectious diseases or oncology and the majority used electronic health records/electronic medical records data and cohort studies data. Different statistical methods were used to address confounding at baseline and selection bias, predominantly conditioning on the confounders (N = 18/49, 37%) and inverse probability of censoring weighting (N = 7/20, 35%) respectively. Different approaches were used to address immortal time bias, assigning individuals to treatment strategies at start of follow-up based on their data available at that specific time (N = 21, 55%), using the sequential trial emulations approach (N = 11, 29%) or the cloning approach (N = 6, 16%).

Conclusion

Different methods can be leveraged to address (A) confounding bias, (B) immortal time bias, and (C) selection bias. When working with observational data, and if possible, the 'target trial' framework should be used as it provides a structured conceptual approach to observational research.",,doi:https://doi.org/10.1186/s12874-023-02000-9 -36874571,https://doi.org/10.12688/wellcomeopenres.17981.1,Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.,"Hoskins S, Beale S, Nguyen V, Fragaszy E, Navaratnam AMD, Smith C, French C, Kovar J, Byrne T, Fong WLE, Geismar C, Patel P, Yavlinksy A, Johnson AM, Aldridge RW, Hayward A, Virus Watch Collaborative.",,Wellcome open research,2022,2022-08-03,Y,Transmission; Activities; Pandemic; Work; Public Transport; Shopping; Lockdown; Covid-19; Sars-cov-2,,,"Background: ""Lockdowns"" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.  Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.",,doi:https://doi.org/10.12688/wellcomeopenres.17981.1; html:https://europepmc.org/articles/PMC9975411; pdf:https://europepmc.org/articles/PMC9975411?pdf=render 35308936,https://doi.org/,Mapping the Read2/CTV3 controlled clinical terminologies to Phecodes in UK Biobank primary care electronic health records: implementation and evaluation.,"Denaxas S, Liu G, Feng Q, Fatemifar G, Bastarache L, Kerchberger EV, Hingorani AD, Lumbers T, Peterson JF, Wei WQ, Hemingway H.",,AMIA ... Annual Symposium proceedings. AMIA Symposium,2021,2021-01-01,N,,,,"Objective: To establish and validate mappings between primary care clinical terminologies (Read Version 2, Clinical Terms Version 3) and Phecodes. Methods: We processed 123,662,421 primary care events from 230,096 UK Biobank (UKB) participants. We assessed the validity of the primary care-derived Phecodes by conducting PheWAS analyses for seven pre-selected SNPs in the UKB and compared with estimates from BioVU. Results: We mapped 92% of Read2 (n=10,834) and 91% of CTV3 (n=21,988) to 1,449 and 1,490 Phecodes. UKB PheWAS using Phecodes from primary care EHR and hospitalizations replicated all (n=22) previously-reported genotype-phenotype associations. When limiting Phecodes to primary care EHR, replication was 81% (n=18). Conclusion: We introduced a first version of mappings from Read2/CTV3 to Phecodes. The reference list of diseases provided by Phecodes can be extended, enabling researchers to leverage primary care EHR for high-throughput discovery research.",,html:https://europepmc.org/articles/PMC8861677; pdf:https://europepmc.org/articles/PMC8861677?pdf=render +36874571,https://doi.org/10.12688/wellcomeopenres.17981.1,Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.,"Hoskins S, Beale S, Nguyen V, Fragaszy E, Navaratnam AMD, Smith C, French C, Kovar J, Byrne T, Fong WLE, Geismar C, Patel P, Yavlinksy A, Johnson AM, Aldridge RW, Hayward A, Virus Watch Collaborative.",,Wellcome open research,2022,2022-08-03,Y,Transmission; Activities; Pandemic; Work; Public Transport; Shopping; Lockdown; Covid-19; Sars-cov-2,,,"Background: ""Lockdowns"" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.  Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.",,doi:https://doi.org/10.12688/wellcomeopenres.17981.1; html:https://europepmc.org/articles/PMC9975411; pdf:https://europepmc.org/articles/PMC9975411?pdf=render 36994768,https://doi.org/10.1002/cphy.c210037,Autonomic Cardiovascular Control in Health and Disease.,"Karim S, Chahal A, Khanji MY, Petersen SE, Somers VK.",,Comprehensive Physiology,2023,2023-03-30,N,,,,"Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.",,doi:https://doi.org/10.1002/cphy.c210037 33952557,https://doi.org/10.1136/bmjopen-2021-049964,Study protocol of the Edinburgh and Lothian Virus Intervention Study in Kids: a randomised controlled trial of hypertonic saline nose drops in children with upper respiratory tract infections (ELVIS Kids).,"Ramalingam S, Graham C, Oatey K, Rayson P, Stoddart A, Sheikh A, Cunningham S, ELVIS Kids Trial Investigators.",,BMJ open,2021,2021-05-05,Y,Virology; Community Child Health; Neonatology; Primary Care; Paediatric Infectious Disease & Immunisation,,,"

Introduction

Edinburgh and Lothians' Viral Intervention Study Kids is a parallel, open-label, randomised controlled trial of hypertonic saline (HS) nose drops (~2.6% sodium chloride) vs standard care in children <7 years of age with symptoms of an upper respiratory tract infection (URTI).

Methods and analysis

Children are recruited prior to URTI or within 48 hours of developing URTI symptoms by advertising in areas such as local schools/nurseries, health centres/hospitals, recreational facilities, public events, workplaces, local/social media. Willing parents/guardians, of children <7 years of age will be asked to contact the research team at their local site. Children will be randomised to either a control arm (standard symptomatic care), or intervention arm (three drops/nostril of HS, at least four times a day, until 24 hours after asymptomatic or a maximum of 28 days). All participants are requested to provide a nasal swab at the start of the study (intervention arm: before HS drops) and then daily for four more days. Parent/guardian complete a validated daily diary, an end of illness diary, a satisfaction questionnaire and a wheeze questionnaire (day 28). The parent/guardian of a child in the intervention arm is taught to prepare HS nose drops. Parent/guardian of children asymptomatic at recruitment are requested to inform the research team within 48 hours of their child developing an URTI and follow the instructions already provided. The day 28 questionnaire determines if the child experienced a wheeze following illness. Participation in the study ends on day 28.

Ethics and dissemination

The study has been approved by the West of Scotland Research Ethics Service (18/WS/0080). It is cosponsored by Academic and Clinical Central Office for Research and Development-a partnership between the University of Edinburgh and National Health Service Lothian Health Board. The findings will be disseminated through peer-reviewed publications, conference presentations and via the study website.

Trial registration number

NCT03463694.",,doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render 35780515,https://doi.org/10.1016/j.epidem.2022.100604,Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number.,"Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S.",,Epidemics,2022,2022-06-22,Y,Cross-sectional study; Reproduction Number; Covid-19; Sars-cov-2; Bayesian P-Spline,,,"The time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England's second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.",,doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render @@ -559,22 +560,22 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 33577558,https://doi.org/10.1371/journal.pmed.1003497,"Association of socioeconomic deprivation with asthma care, outcomes, and deaths in Wales: A 5-year national linked primary and secondary care cohort study.","Alsallakh MA, Rodgers SE, Lyons RA, Sheikh A, Davies GA.",,PLoS medicine,2021,2021-02-12,Y,,,,"

Background

Socioeconomic deprivation is known to be associated with worse outcomes in asthma, but there is a lack of population-based evidence of its impact across all stages of patient care. We investigated the association of socioeconomic deprivation with asthma-related care and outcomes across primary and secondary care and with asthma-related death in Wales.

Methods and findings

We constructed a national cohort, identified from 76% (2.4 million) of the Welsh population, of continuously treated asthma patients between 2013 and 2017 using anonymised, person-level, linked, routinely collected primary and secondary care data in the Secure Anonymised Information Linkage (SAIL) Databank. We investigated the association between asthma-related health service utilisation, prescribing, and deaths with the 2011 Welsh Index of Multiple Deprivation (WIMD) and its domains. We studied 106,926 patients (534,630 person-years), 56.3% were female, with mean age of 47.5 years (SD = 20.3). Compared to the least deprived patients, the most deprived patients had slightly fewer total asthma-related primary care consultations per patient (incidence rate ratio [IRR] = 0.98, 95% CI 0.97-0.99, p-value < 0.001), slightly fewer routine asthma reviews (IRR = 0.98, 0.97-0.99, p-value < 0.001), lower controller-to-total asthma medication ratios (AMRs; 0.50 versus 0.56, p-value < 0.001), more asthma-related accident and emergency (A&E) attendances (IRR = 1.27, 1.10-1.46, p-value = 0.001), more asthma emergency admissions (IRR = 1.56, 1.39-1.76, p-value < 0.001), longer asthma-related hospital stay (IRR = 1.64, 1.39-1.94, p-value < 0.001), and were at higher risk of asthma-related death (risk ratio of deaths with any mention of asthma 1.56, 1.18-2.07, p-value = 0.002). Study limitations include the deprivation index being area based and the potential for residual confounders and mediators.

Conclusions

In this study, we observed that the most deprived asthma patients in Wales had different prescribing patterns, more A&E attendances, more emergency hospital admissions, and substantially higher risk of death. Interventions specifically designed to improve treatment and outcomes for these disadvantaged groups are urgently needed.",,doi:https://doi.org/10.1371/journal.pmed.1003497; html:https://europepmc.org/articles/PMC7880491; pdf:https://europepmc.org/articles/PMC7880491?pdf=render 33971933,https://doi.org/10.1186/s13063-021-05295-5,Accessing routinely collected health data to improve clinical trials: recent experience of access.,"Macnair A, Love SB, Murray ML, Gilbert DC, Parmar MKB, Denwood T, Carpenter J, Sydes MR, Langley RE, Cafferty FH.",,Trials,2021,2021-05-10,Y,Clinical Trials; Electronic Health Records; Data Accessibility; Routinely Collected Data,,,"

Background

Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.

Methods

This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams' application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).

Results

The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.

Conclusions

Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.",,doi:https://doi.org/10.1186/s13063-021-05295-5; html:https://europepmc.org/articles/PMC8108438; pdf:https://europepmc.org/articles/PMC8108438?pdf=render 35440469,https://doi.org/10.3399/bjgp.2022.0083,"Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.","Dorward J, Yu LM, Hayward G, Saville BR, Gbinigie O, Van Hecke O, Ogburn E, Evans PH, Thomas NP, Patel MG, Richards D, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Shanyinde M, de Lusignan S, Andersson MI, Butler CC, Hobbs FR, PRINCIPLE Trial Collaborative Group.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Colchicine; Community; Primary Health Care; Randomised Controlled Trial; Covid-19,,,"

Background

Colchicine has been proposed as a COVID-19 treatment.

Aim

To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.

Design and setting

Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).

Method

Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models.

Results

The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4).

Conclusion

Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render -36808078,https://doi.org/10.1136/pn-2021-003286,Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.,"Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.",,Practical neurology,2023,2023-02-20,Y,Clinical Neurology,,,"Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.",,doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render; pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf 35485805,https://doi.org/10.1017/s003329172200109x,Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.,"Ma R, Romano E, Ashworth M, Yadegarfar ME, Dregan A, Ronaldson A, de Oliveira C, Jacobs R, Stewart R, Stubbs B.",,Psychological medicine,2022,2022-04-29,Y,Mortality; Schizophrenia; Psychosis; Physical Health; Multimorbidity,,,"

Background

People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.

Methods

People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.

Results

The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters.

Conclusion

The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.",,doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?pdf=render; pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/BDE3DC6059EB59B00B2E0CD892963804/S003329172200109Xa.pdf/div-class-title-multimorbidity-clusters-among-people-with-serious-mental-illness-a-representative-primary-and-secondary-data-linkage-cohort-study-div.pdf +36808078,https://doi.org/10.1136/pn-2021-003286,Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.,"Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.",,Practical neurology,2023,2023-02-20,Y,Clinical Neurology,,,"Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.",,doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render; pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf 34308306,https://doi.org/10.1016/j.eclinm.2021.100888,The BCD Triage Sieve outperforms all existing major incident triage tools: Comparative analysis using the UK national trauma registry population.,"Malik NS, Chernbumroong S, Xu Y, Vassallo J, Lee J, Bowley DM, Hodgetts T, Moran CG, Lord JM, Belli A, Keene D, Foster M, Gkoutos GV.",,EClinicalMedicine,2021,2021-05-15,Y,ramp; Disaster; Start; Military Medicine; Major Incident; Triage; Injury Severity Score; Mass Casualty; Major Trauma; Prehospital Medicine; Life-saving Intervention; Careflight; Jumpstart; Bcd Triage Sieve; Mimms; Mptt-24; Mstart,,,"

Background

Natural disasters, conflict, and terrorism are major global causes of death and disability. Central to the healthcare response is triage, vital to ensure the right care is provided to the right patient at the right time. The ideal triage tool has high sensitivity for the highest priority (P1) patients with acceptably low over-triage. This study compared the performance of major incident triage tools in predicting P1 casualty status in adults in the prospective UK Trauma Audit and Research Network (TARN) registry.

Methods

TARN patients aged 16+ years (January 2008-December 2017) were included. Ten existing triage tools were applied using patients' first recorded pre-hospital physiology. Patients were subsequently assigned triage categories (P1, P2, P3, Expectant or Dead) based on pre-defined, intervention-based criteria. Tool performance was assessed by comparing tool-predicted and intervention-based priority status.

Findings

195,709 patients were included; mortality was 7·0% (n=13,601); median Injury Severity Score (ISS) was 9 (IQR 9-17); 97·1% sustained blunt injuries. 22,144 (11·3%) patients fulfilled intervention-based criteria for P1 status, exhibiting higher mortality (12·8% vs. 5·0%, p<0.001), increased intensive care requirement (52·4% vs 5·0%, p<0.001), and more severe injuries (median ISS 21 vs 9, p<0.001) compared with P2 patients.In 16-64 year olds, the highest performing tool was the Battlefield Casualty Drills (BCD) Triage Sieve (Prediction of P1 status: 70·4% sensitivity, over-triage 70·9%, area under the receiver operating curve (AUC) 0·068 [95%CI 0·676-0·684]). The UK National Ambulance Resilience Unit (NARU) Triage Sieve had sensitivity of 44·9%; over-triage 56·4%; AUC 0·666 (95%CI 0·662-0·670). All tools performed poorly amongst the elderly (65+ years).

Interpretation

The BCD Triage Sieve performed best in this nationally representative population; we recommend it supersede the NARU Triage Sieve as the UK primary major incident triage tool. Validated triage category definitions are recommended for appraising future major incidents.

Funding

This study is funded by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. GVG also acknowledges support from the MRC Heath Data Research UK (HDRUK/CFC/01). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the Ministry of Defence.",,doi:https://doi.org/10.1016/j.eclinm.2021.100888; html:https://europepmc.org/articles/PMC8257989; pdf:https://europepmc.org/articles/PMC8257989?pdf=render 35932242,https://doi.org/10.1093/ageing/afac176,"Annual risk of falls resulting in emergency department and hospital attendances for older people: an observational study of 781,081 individuals living in Wales (United Kingdom) including deprivation, frailty and dementia diagnoses between 2010 and 2020.","Hollinghurst R, Williams N, Pedrick-Case R, North L, Long S, Fry R, Hollinghurst J.",,Age and ageing,2022,2022-08-01,Y,Frailty; Dementia; Falls; Older People; Covid-19,,,"

Background

falls are common in older people, but associations between falls, dementia and frailty are relatively unknown. The impact of the COVID-19 pandemic on falls admissions has not been studied.

Aim

to investigate the impact of dementia, frailty, deprivation, previous falls and the differences between years for falls resulting in an emergency department (ED) or hospital admission.

Study design

longitudinal cross-sectional observational study.

Setting

older people (aged 65+) resident in Wales between 1 January 2010 and 31 December 2020.

Methods

we created a binary (yes/no) indicator for a fall resulting in an attendance to an ED, hospital or both, per person, per year. We analysed the outcomes using multilevel logistic and multinomial models.

Results

we analysed a total of 5,141,244 person years of data from 781,081 individuals. Fall admission rates were highest in 2012 (4.27%) and lowest in 2020 (4.27%). We found an increased odds ratio (OR [95% confidence interval]) of a fall admission for age (1.05 [1.05, 1.05] per year of age), people with dementia (2.03 [2.00, 2.06]) and people who had a previous fall (2.55 [2.51, 2.60]). Compared with fit individuals, those with frailty had ORs of 1.60 [1.58, 1.62], 2.24 [2.21, 2.28] and 2.94 [2.89, 3.00] for mild, moderate and severe frailty respectively. Reduced odds were observed for males (0.73 [0.73, 0.74]) and less deprived areas; most deprived compared with least OR 0.75 [0.74, 0.76].

Conclusions

falls prevention should be targeted to those at highest risk, and investigations into the reduction in admissions in 2020 is warranted.",,doi:https://doi.org/10.1093/ageing/afac176; html:https://europepmc.org/articles/PMC9356534; pdf:https://europepmc.org/articles/PMC9356534?pdf=render 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"

Objective

To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.

Design

Cross-sectional study.

Setting

East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.

Participants

EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.

Main outcome measure

COVID-19 incidence and mortality.

Results

Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).

Conclusions

In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render +35996157,https://doi.org/10.1186/s13059-022-02745-4,Comparative transcriptome in large-scale human and cattle populations.,"Yao Y, Liu S, Xia C, Gao Y, Pan Z, Canela-Xandri O, Khamseh A, Rawlik K, Wang S, Li B, Zhang Y, Pairo-Castineira E, D'Mellow K, Li X, Yan Z, Li CJ, Yu Y, Zhang S, Ma L, Cole JB, Ross PJ, Zhou H, Haley C, Liu GE, Fang L, Tenesa A.",,Genome biology,2022,2022-08-22,Y,Rna-seq; Gene Co-expression; Comparative Transcriptome; Inter-individual Variability; Heritability Enrichment,,,"

Background

Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes.

Results

Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues.

Conclusions

In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.",,doi:https://doi.org/10.1186/s13059-022-02745-4; html:https://europepmc.org/articles/PMC9394047; pdf:https://europepmc.org/articles/PMC9394047?pdf=render 37526977,https://doi.org/10.5830/cvja-2023-037,Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.,"Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,Cardiovascular journal of Africa,2023,2023-07-25,N,Screening; Dilated cardiomyopathy; First‐degree Relatives,,,"

Background

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim

The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Methods

We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.

Results

We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (± SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 ± 11.5 ml) compared to relatives without DCM (50 ± 11.5) (p = 0.001).

Conclusion

First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.",,doi:https://doi.org/10.5830/CVJA-2023-037 36794597,https://doi.org/10.1111/trf.17277,Impact of a post-donation hemoglobin testing strategy on efficiency and safety of whole blood donation in England: A modeling study.,"Kim LG, Bolton T, Sweeting MJ, Bell S, Fahle S, McMahon A, Walker M, Ferguson E, Miflin G, Roberts DJ, Di Angelantonio E, Wood AM.",,Transfusion,2023,2023-02-16,N,Blood Donation; Simulation Modeling; Low Hemoglobin Deferral; Post-donation Testing,,,"

Background

Deferrals due to low hemoglobin are time-consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter-donation intervals.

Study design and methods

We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter-donation intervals using ""post-donation"" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre-donation testing with fixed intervals of 12-weeks for men and 16-weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter-donation intervals were defined using mixed-effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.

Results

The model had generally good internal validation, with predicted events similar to those observed. Over 1 year, a personalized strategy requiring ≥90% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.

Discussion

Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",,doi:https://doi.org/10.1111/trf.17277; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277 -35996157,https://doi.org/10.1186/s13059-022-02745-4,Comparative transcriptome in large-scale human and cattle populations.,"Yao Y, Liu S, Xia C, Gao Y, Pan Z, Canela-Xandri O, Khamseh A, Rawlik K, Wang S, Li B, Zhang Y, Pairo-Castineira E, D'Mellow K, Li X, Yan Z, Li CJ, Yu Y, Zhang S, Ma L, Cole JB, Ross PJ, Zhou H, Haley C, Liu GE, Fang L, Tenesa A.",,Genome biology,2022,2022-08-22,Y,Rna-seq; Gene Co-expression; Comparative Transcriptome; Inter-individual Variability; Heritability Enrichment,,,"

Background

Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes.

Results

Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues.

Conclusions

In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.",,doi:https://doi.org/10.1186/s13059-022-02745-4; html:https://europepmc.org/articles/PMC9394047; pdf:https://europepmc.org/articles/PMC9394047?pdf=render 36377225,https://doi.org/10.1177/18333583221135710,Concordance between coding sources of burn size and depth across Australian and New Zealand specialist burn services.,"Perkins M, Cleland H, Gabbe BJ, Tracy LM.",,Health information management : journal of the Health Information Management Association of Australia,2022,2022-11-14,N,Burns; Australia; New Zealand; Registries; Health Information Management; International Classification Of Diseases; Clinical Coding,,,"

Background

The percentage of total body surface area (%TBSA) burned and burn depth provide valuable information on burn injury severity.

Objective

This study investigated the concordance between The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and expert burn clinicians in assessing burn injury severity.

Method

We conducted a retrospective population-based review of all patients who sustained a burn injury between July 1, 2009, and June 30, 2019, requiring admission into a specialist burn service across Australia and New Zealand. The %TBSA burned (including the percentage of full thickness burns) recorded by expert burn clinicians within the Burns Registry of Australia and New Zealand (BRANZ) were compared to ICD-10-AM coding.

Results

20,642 cases (71.5%) with ICD-10-AM code data were recorded. Overall, kappa scores (95% confidence interval [CI]) for burn size ranged from 0.64 (95% CI 0.63-0.66) to 0.86 (95% CI 0.78-0.94) indicating substantial to almost perfect agreement across all %TBSA groups. When stratified by depth, the lowest agreement was observed for < 10% TBSA and < 10% full thickness (kappa 0.03; 95% CI 0.02-0.04) and the highest agreement was observed for burns of ≥ 90% TBSA and ≥ 90% full thickness (kappa 0.72; 95% CI 0.58-0.85).

Conclusion

Overall, there was substantial agreement between the BRANZ and ICD-10-AM coded data for %TBSA classification. When %TBSA classification was stratified by burn depth, greater agreement was observed for larger and deeper burns compared with smaller and superficial burns.

Implications

Greater consistency in the classification of burns is needed.",,doi:https://doi.org/10.1177/18333583221135710 35172999,https://doi.org/10.1136/bmjopen-2021-052911,Can natural language processing models extract and classify instances of interpersonal violence in mental healthcare electronic records: an applied evaluative study.,"Botelle R, Bhavsar V, Kadra-Scalzo G, Mascio A, Williams MV, Roberts A, Velupillai S, Stewart R.",,BMJ open,2022,2022-02-16,Y,Psychiatry; Mental health; Public Health; Health Informatics,,,"

Objective

This paper evaluates the application of a natural language processing (NLP) model for extracting clinical text referring to interpersonal violence using electronic health records (EHRs) from a large mental healthcare provider.

Design

A multidisciplinary team iteratively developed guidelines for annotating clinical text referring to violence. Keywords were used to generate a dataset which was annotated (ie, classified as affirmed, negated or irrelevant) for: presence of violence, patient status (ie, as perpetrator, witness and/or victim of violence) and violence type (domestic, physical and/or sexual). An NLP approach using a pretrained transformer model, BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) was fine-tuned on the annotated dataset and evaluated using 10-fold cross-validation.

Setting

We used the Clinical Records Interactive Search (CRIS) database, comprising over 500 000 de-identified EHRs of patients within the South London and Maudsley NHS Foundation Trust, a specialist mental healthcare provider serving an urban catchment area.

Participants

Searches of CRIS were carried out based on 17 predefined keywords. Randomly selected text fragments were taken from the results for each keyword, amounting to 3771 text fragments from the records of 2832 patients.

Outcome measures

We estimated precision, recall and F1 score for each NLP model. We examined sociodemographic and clinical variables in patients giving rise to the text data, and frequencies for each annotated violence characteristic.

Results

Binary classification models were developed for six labels (violence presence, perpetrator, victim, domestic, physical and sexual). Among annotations affirmed for the presence of any violence, 78% (1724) referred to physical violence, 61% (1350) referred to patients as perpetrator and 33% (731) to domestic violence. NLP models' precision ranged from 89% (perpetrator) to 98% (sexual); recall ranged from 89% (victim, perpetrator) to 97% (sexual).

Conclusions

State of the art NLP models can extract and classify clinical text on violence from EHRs at acceptable levels of scale, efficiency and accuracy.",,doi:https://doi.org/10.1136/bmjopen-2021-052911; html:https://europepmc.org/articles/PMC8852656; pdf:https://europepmc.org/articles/PMC8852656?pdf=render -37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render 34007896,https://doi.org/10.23889/ijpds.v6i1.1387,"A retrospective epidemiological study of type 1 diabetes mellitus in wales, UK between 2008 and 2018.","Rafferty J, Stephens JW, Atkinson MD, Luzio SD, Akbari A, Gregory JW, Bain S, Owens DR, Thomas RL.",,International journal of population data science,2021,2021-04-15,Y,Diabetes mellitus; epidemiology; Electronic Health Records,,,"

Introduction

Studies of prevalence and the demographic profile of type 1 diabetes are challenging because of the relative rarity of the condition, however, these outcomes can be determined using routine healthcare data repositories. Understanding the epidemiology of type 1 diabetes allows for targeted interventions and care of this life-affecting condition.

Objectives

To describe the prevalence, incidence and demographics of persons with type 1 diabetes diagnosed in Wales, UK, using the Secure Anonymised Information Linkage (SAIL) Databank.

Methods

Data derived from primary and secondary care throughout Wales available in the SAIL Databank were used to identify people with type 1 diabetes to determine the prevalence and incidence of type 1 diabetes over a 10 year period (2008-18) and describe the demographic and clinical characteristics of this population by age, socioeconomic deprivation and settlement type. The seasonal variation in incidence rates was also examined.

Results

The prevalence of type 1 diabetes in 2018 was 0.32% in the whole population, being greater in men compared to women (0.35% vs 0.28% respectively); highest in those aged 15-29 years (0.52%) and living in the most socioeconomically deprived areas (0.38%). The incidence of type 1 diabetes over 10 years was 14.0 cases/100,000 people/year for the whole population of Wales. It was highest in children aged 0-14 years (33.6 cases/100,000 people/year) and areas of high socioeconomic deprivation (16.8 cases/100,000 people/year) and least in those aged 45-60 years (6.5 cases/100,000 people/year) and in areas of low socioeconomic deprivation (11.63 cases/100,000 people/year). A seasonal trend in the diagnoses of type 1 diabetes was observed with higher incidence in winter months.

Conclusion

This nation-wide retrospective epidemiological study using routine data revealed that the incidence of type 1 diabetes in Wales was greatest in those aged 0-14 years with a higher incidence and prevalence in the most deprived areas. These findings illustrate the need for health-related policies targeted at high deprivation areas to include type 1 diabetes in their remit.",,doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render +37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render 34148732,https://doi.org/10.1016/j.bja.2021.05.001,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,British journal of anaesthesia,2021,2021-06-18,Y,Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19,,,"

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.",,doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render 34265229,https://doi.org/10.1177/01410768211032850,"Symptoms, complications and management of long COVID: a review.","Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, Haroon S, Price G, Davies EH, Nirantharakumar K, Sapey E, Calvert MJ, TLC Study Group.",,Journal of the Royal Society of Medicine,2021,2021-07-15,Y,Infectious diseases; epidemiology; Public Health; Respiratory Medicine; Health Service Research; Covid-19; Post-Covid-19 Syndrome; Persistent Covid-19 Symptoms; Long Covid,,,"Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.",,doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render -36567336,https://doi.org/10.1186/s12872-022-03005-w,Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.,"Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.",,BMC cardiovascular disorders,2022,2022-12-26,Y,Dyspnea; Machine Learning; Hfpef,,,"

Background

Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a data-driven diagnostic model to predict from electronic health records (EHR) the likelihood of HFpEF among patients with unexplained dyspnea and preserved left ventricular EF.

Methods and results

The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF (cases), non-HF (control cohort I), or HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting HFpEF had an AUROC of 90% (P < 0.001) and average precision of 74%.

Conclusion

This diagnostic signature enables discrimination of HFpEF from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.",,doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render 34534697,https://doi.org/10.1016/j.jbi.2021.103916,Ranking sets of morbidities using hypergraph centrality.,"Rafferty J, Watkins A, Lyons J, Lyons RA, Akbari A, Peek N, Jalali-Najafabadi F, Ba Dhafari T, Pate A, Martin GP, Bailey R.",,Journal of biomedical informatics,2021,2021-09-15,Y,Network Analysis; Hypergraph; Multi-morbidity,,,"Multi-morbidity, the health state of having two or more concurrent chronic conditions, is becoming more common as populations age, but is poorly understood. Identifying and understanding commonly occurring sets of diseases is important to inform clinical decisions to improve patient services and outcomes. Network analysis has been previously used to investigate multi-morbidity, but a classic application only allows for information on binary sets of diseases to contribute to the graph. We propose the use of hypergraphs, which allows for the incorporation of data on people with any number of conditions, and also allows us to obtain a quantitative understanding of the centrality, a measure of how well connected items in the network are to each other, of both single diseases and sets of conditions. Using this framework we illustrate its application with the set of conditions described in the Charlson morbidity index using data extracted from routinely collected population-scale, patient level electronic health records (EHR) for a cohort of adults in Wales, UK. Stroke and diabetes were found to be the most central single conditions. Sets of diseases featuring diabetes; diabetes with Chronic Pulmonary Disease, Renal Disease, Congestive Heart Failure and Cancer were the most central pairs of diseases. We investigated the differences between results obtained from the hypergraph and a classic binary graph and found that the centrality of diseases such as paraplegia, which are connected strongly to a single other disease is exaggerated in binary graphs compared to hypergraphs. The measure of centrality is derived from the weighting metrics calculated for disease sets and further investigation is needed to better understand the effect of the metric used in identifying the clinical significance and ranked centrality of grouped diseases. These initial results indicate that hypergraphs can be used as a valuable tool for analysing previously poorly understood relationships and information available in EHR data.",,doi:https://doi.org/10.1016/j.jbi.2021.103916; html:https://europepmc.org/articles/PMC8524321 +36567336,https://doi.org/10.1186/s12872-022-03005-w,Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.,"Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.",,BMC cardiovascular disorders,2022,2022-12-26,Y,Dyspnea; Machine Learning; Hfpef,,,"

Background

Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a data-driven diagnostic model to predict from electronic health records (EHR) the likelihood of HFpEF among patients with unexplained dyspnea and preserved left ventricular EF.

Methods and results

The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF (cases), non-HF (control cohort I), or HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting HFpEF had an AUROC of 90% (P < 0.001) and average precision of 74%.

Conclusion

This diagnostic signature enables discrimination of HFpEF from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.",,doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render 35813280,https://doi.org/10.1016/s2666-7568(22)00118-0,Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study.,"Tut G, Lancaster T, Sylla P, Butler MS, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Ayodele M, Bone D, Tut E, Bruton R, Krutikov M, Giddings R, Shrotri M, Azmi B, Fuller C, Baynton V, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"

Background

Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs).

Methods

In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified.

Findings

Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39-61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80-92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72-100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds vs 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89-374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30-206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production.

Interpretation

These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination.

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(22)00118-0; html:https://europepmc.org/articles/PMC9252532; pdf:https://europepmc.org/articles/PMC9252532?pdf=render 36447757,https://doi.org/10.1136/gpsych-2022-100819,Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.,"Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",,General psychiatry,2022,2022-11-04,Y,Schizophrenia; Life style; Mental Health Services,,,"

Background

People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.

Aims

In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.

Methods

We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.

Results

Of 11 900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).

Conclusions

Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",,doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render 35802764,https://doi.org/10.7189/jogh.12.05025,COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes from Delta AY.4.2: Cohort and test-negative study of 5.4 million individuals in Scotland.,"Kerr S, Vasileiou E, Robertson C, Sheikh A.",,Journal of global health,2022,2022-07-09,Y,,,,"

Background

In July 2021, a new variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the Delta lineage was detected in the United Kingdom (UK), named AY.4.2 or ""Delta plus"". By October 2021, the AY.4.2 variant accounted for approximately 10-11% of cases in the UK. AY.4.2 was designated as a variant under investigation by the UK Health and Security Agency on 20 October 2021. This study aimed to investigate vaccine effectiveness (VE) against symptomatic COVID-19 (Coronavirus disease 2019) infection and COVID-19 hospitalisation/death for the AY.4.2 variant.

Methods

We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE-II) platform to estimate the VE of the ChAdOx1, BNT162b2, and mRNA-1273 vaccines against symptomatic infection and severe COVID-19 outcomes in adults. The study was conducted from June 8 to October 25, 2021. We used a test-negative design (TND) to estimate VE against reverse transcriptase polymerase chain reaction (RT-PCR) confirmed symptomatic SARS-CoV-2 infection while adjusting for sex, socioeconomic status, number of coexisting conditions, and splines in time and age. We also performed a cohort study using a Cox proportional hazards model to estimate VE against a composite outcome of COVID-19 hospital admission or death, with the same adjustments.

Results

We found an overall VE against symptomatic SARS-CoV-2 infection due to AY.4.2 of 73% (95% confidence interval (CI) = 62-81) for >14 days post-second vaccine dose. Good protection against AY.4.2 symptomatic infection was observed for BNT162b2, ChAdOx1, and mRNA-1273. In unvaccinated individuals, the hazard ratio (HR) for COVID-19 hospital admission or death from AY.4.2 among community detected cases was 1.77 (95% CI = 1.02-3.07) relative to unvaccinated individuals who were infected with Delta, after adjusting for multiple potential confounders. VE against AY.4.2 COVID-19 admissions or deaths was 87% (95% CI = 74-93) >28 days post-second vaccination relative to unvaccinated.

Conclusions

We found that AY.4.2 was associated with an increased risk of COVID-19 hospitalisations or deaths in unvaccinated individuals compared with Delta and that vaccination provided substantial protection against symptomatic SARS-CoV-2 and severe COVID-19 outcomes following Delta AY.4.2 infection. High levels of vaccine uptake and protection offered by existing vaccines, as well as the rapid emergence of the Omicron variant may have contributed to the AY.4.2 variant never progressing to a variant of concern.",,doi:https://doi.org/10.7189/jogh.12.05025; html:https://europepmc.org/articles/PMC9269984; pdf:https://europepmc.org/articles/PMC9269984?pdf=render @@ -592,24 +593,24 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 36773891,https://doi.org/10.1016/j.jinf.2023.02.012,"Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.","Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.",,The Journal of infection,2023,2023-02-10,Y,Health protection; Public Health; Covid-19,,,"

Objective

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

Design

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

Setting

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

Participants

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

Interventions

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

Main outcome measures

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

Statistical analysis

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

Results

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

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.",,doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render 36001371,https://doi.org/10.2196/38122,Deployment of a Free-Text Analytics Platform at a UK National Health Service Research Hospital: CogStack at University College London Hospitals.,"Noor K, Roguski L, Bai X, Handy A, Klapaukh R, Folarin A, Romao L, Matteson J, Lea N, Zhu L, Asselbergs FW, Wong WK, Shah A, Dobson RJ.",,JMIR medical informatics,2022,2022-08-24,Y,Information Retrieval; Natural Language Processing; Text Mining; Electronic Health Record System; Clinical Support,,,"

Background

As more health care organizations transition to using electronic health record (EHR) systems, it is important for these organizations to maximize the secondary use of their data to support service improvement and clinical research. These organizations will find it challenging to have systems capable of harnessing the unstructured data fields in the record (clinical notes, letters, etc) and more practically have such systems interact with all of the hospital data systems (legacy and current).

Objective

We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).

Methods

At UCLH, we have deployed the CogStack platform, an information retrieval platform with natural language processing capabilities. The platform addresses the problem of data ingestion and harmonization from multiple data sources using the Apache NiFi module for managing complex data flows. The platform also facilitates the extraction of structured data from free-text records through use of the MedCAT natural language processing library. Finally, data science tools are made available to support data scientists and the development of downstream applications dependent upon data ingested and analyzed by CogStack.

Results

The platform has been deployed at the hospital, and in particular, it has facilitated a number of research and service evaluation projects. To date, we have processed over 30 million records, and the insights produced from CogStack have informed a number of clinical research use cases at the hospital.

Conclusions

The CogStack platform can be configured to handle the data ingestion and harmonization challenges faced by a hospital. More importantly, the platform enables the hospital to unlock important clinical information from the unstructured portion of the record using natural language processing technology.",,doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582 33587202,https://doi.org/10.1007/s10654-021-00722-y,COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors.,"Elliott J, Bodinier B, Whitaker M, Delpierre C, Vermeulen R, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,European journal of epidemiology,2021,2021-02-15,Y,Risk factor; Prospective Cohort; Uk Biobank; Sars-cov-2; Covid-19 Mortality,,,"Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18-3.49] per S.D. [8.1 years], p = 2.6 × 10-17), male sex (OR = 1.47 [1.26-1.73], p = 1.3 × 10-6) and Black versus White ethnicity (OR = 1.21 [1.12-1.29], p = 3.0 × 10-7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin-angiotensin-aldosterone system inhibitors may be explained by the aforementioned factors.",,doi:https://doi.org/10.1007/s10654-021-00722-y; html:https://europepmc.org/articles/PMC7882869; pdf:https://europepmc.org/articles/PMC7882869?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00722-y.pdf -37635632,https://doi.org/10.1111/aor.14628,Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.,"Numan L, Wösten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.",,Artificial organs,2023,2023-08-28,N,Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters,,,"

Background

Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).

Methods

18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.

Results

A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19).

Conclusions

A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.",,doi:https://doi.org/10.1111/aor.14628 34249083,https://doi.org/10.3389/fgene.2021.652878,Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.,"Soto-Pedre E, Siddiqui MK, Maroteau C, Dawed AY, Doney AS, Palmer CNA, Pearson ER, Leese GP.",,Frontiers in genetics,2021,2021-06-23,Y,Genetics; Insulin receptor; Hypothyroidism; Atrial fibrillation; Thyroid Hormone Replacement Therapy,,,"

Aims

Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.

Methods and results

A retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).

Conclusion

Homozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.",,doi:https://doi.org/10.3389/fgene.2021.652878; html:https://europepmc.org/articles/PMC8260687; pdf:https://europepmc.org/articles/PMC8260687?pdf=render 36102151,https://doi.org/10.1210/clinem/dgac527,Identification of 4 New Loci Associated With Primary Hyperparathyroidism (PHPT) and a Polygenic Risk Score for PHPT.,"Soto-Pedre E, Newey PJ, Srinivasan S, Siddiqui MK, Palmer CNA, Leese GP.",,The Journal of clinical endocrinology and metabolism,2022,2022-11-01,Y,Genetics; Genome-wide Association Study; Primary Hyperparathyroidism; Polygenic Risk Score,,,"

Context

A hypothesis-free genetic association analysis has not been reported for patients with primary hyperparathyroidism (PHPT).

Objective

We aimed to investigate genetic associations with PHPT using both genome-wide association study (GWAS) and candidate gene approaches.

Methods

A cross-sectional study was conducted among patients of European White ethnicity recruited in Tayside (Scotland, UK). Electronic medical records were used to identify PHPT cases and controls, and linked to genetic biobank data. Genetic associations were performed by logistic regression models and odds ratios (ORs). The combined effect of the genotypes was researched by genetic risk score (GRS) analysis.

Results

We identified 15 622 individuals for the GWAS that yielded 34 top single-nucleotide variations (formerly single-nucleotide polymorphisms), and LPAR3-rs147672681 reached genome-wide statistical significance (P = 1.2e-08). Using a more restricted PHPT definition, 8722 individuals with data on the GWAS-identified loci were found. Age- and sex-adjusted ORs for the effect alleles of SOX9-rs11656269, SLITRK5-rs185436526, and BCDIN3D-AS1-rs2045094 showed statistically significant increased risks (P < 1.5e-03). GRS analysis of 5482 individuals showed an OR of 2.51 (P = 1.6e-04), 3.78 (P = 4.0e-08), and 7.71 (P = 5.3e-17) for the second, third, and fourth quartiles, respectively, compared to the first, and there was a statistically significant linear trend across quartiles (P < 1.0e-04). Results were similar when stratifying by sex.

Conclusion

Using genetic loci discovered in a GWAS of PHPT carried out in a Scottish population, this study suggests new evidence for the involvement of genetic variants at SOX9, SLITRK5, LPAR3, and BCDIN3D-AS1. It also suggests that male and female carriers of greater numbers of PHPT-risk alleles both have a statistically significant increased risk of PHPT.",,doi:https://doi.org/10.1210/clinem/dgac527; html:https://europepmc.org/articles/PMC9693767 -35216844,https://doi.org/10.1016/j.vaccine.2022.02.056,Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.,"Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NRH, Lal S, Eggo RM, Marks M, Chantler T.",,Vaccine,2022,2022-02-17,Y,Qualitative Research; Ethnic Minorities; Coronavirus Vaccine; Localising Services; Public Health Collaboration,,,"Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.",,doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863 +37635632,https://doi.org/10.1111/aor.14628,Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.,"Numan L, Wösten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.",,Artificial organs,2023,2023-08-28,N,Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters,,,"

Background

Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).

Methods

18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.

Results

A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19).

Conclusions

A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.",,doi:https://doi.org/10.1111/aor.14628 33635829,https://doi.org/10.1530/eje-20-1163,Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study.,"Subramanian A, Anand A, Adderley NJ, Okoth K, Toulis KA, Gokhale K, Sainsbury C, O'Reilly MW, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-05-01,Y,,,,"

Objective

Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection.

Design

Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN).

Methods

The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS.

Results

We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63)], P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05-1.56), P = 0.015).

Conclusion

Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic.

Significance statement

Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.",,doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render +35216844,https://doi.org/10.1016/j.vaccine.2022.02.056,Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.,"Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NRH, Lal S, Eggo RM, Marks M, Chantler T.",,Vaccine,2022,2022-02-17,Y,Qualitative Research; Ethnic Minorities; Coronavirus Vaccine; Localising Services; Public Health Collaboration,,,"Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.",,doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863 35580876,https://doi.org/10.1136/bmj-2021-069704,Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,BMJ (Clinical research ed.),2022,2022-05-17,Y,,,,"

Objective

To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.

Design

Observational controlled interrupted time series study.

Setting

UK primary and secondary care.

Participants

515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.

Intervention

Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.

Main outcome measures

The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.

Results

Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.

Conclusions

This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.",,doi:https://doi.org/10.1136/bmj-2021-069704; html:https://europepmc.org/articles/PMC9112858 36150783,https://doi.org/10.1016/s2589-7500(22)00147-9,Data capture and sharing in the COVID-19 pandemic: a cause for concern.,"Dron L, Kalatharan V, Gupta A, Haggstrom J, Zariffa N, Morris AD, Arora P, Park J.",,The Lancet. Digital health,2022,2022-10-01,Y,,,,"Routine health care and research have been profoundly influenced by digital-health technologies. These technologies range from primary data collection in electronic health records (EHRs) and administrative claims to web-based artificial-intelligence-driven analyses. There has been increased use of such health technologies during the COVID-19 pandemic, driven in part by the availability of these data. In some cases, this has resulted in profound and potentially long-lasting positive effects on medical research and routine health-care delivery. In other cases, high profile shortcomings have been evident, potentially attenuating the effect of-or representing a decreased appetite for-digital-health transformation. In this Series paper, we provide an overview of how facets of health technologies in routinely collected medical data (including EHRs and digital data sharing) have been used for COVID-19 research and tracking, and how these technologies might influence future pandemics and health-care research. We explore the strengths and weaknesses of digital-health research during the COVID-19 pandemic and discuss how learnings from COVID-19 might translate into new approaches in a post-pandemic era.",,doi:https://doi.org/10.1016/S2589-7500(22)00147-9; html:https://europepmc.org/articles/PMC9489064; pdf:https://europepmc.org/articles/PMC9489064?pdf=render -36935397,https://doi.org/10.1093/bjs/znad055,Validating a novel natural language processing pathway for automated quality assurance in surgical oncology: incomplete excision rates of 34 955 basal cell carcinomas.,"Ali SR, Dobbs TD, Jovic M, Strafford H, Fonferko-Shadrach B, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.",,The British journal of surgery,2023,2023-08-01,Y,,,,,,doi:https://doi.org/10.1093/bjs/znad055; html:https://europepmc.org/articles/PMC10416688; pdf:https://europepmc.org/articles/PMC10416688?pdf=render; pdf:https://academic.oup.com/bjs/advance-article-pdf/doi/10.1093/bjs/znad055/49561408/znad055.pdf 37105743,https://doi.org/10.3399/bjgp.2022.0353,Impact of COVID-19 pandemic on incidence of long-term conditions in Wales: a population data linkage study using primary and secondary care health records.,"Qi C, Osborne T, Bailey R, Cooper A, Hollinghurst JP, Akbari A, Crowder R, Peters H, Law RJ, Lewis R, Smith D, Edwards A, Lyons RA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-04-27,Y,Diagnosis; Chronic disease; Anxiety; Primary Health Care; Covid-19,,,"

Background

The COVID-19 pandemic has directly and indirectly had an impact on health service provision owing to surges and sustained pressures on the system. The effects of these pressures on the management of long-term or chronic conditions are not fully understood.

Aim

To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.

Design and setting

This was an observational retrospective population data linkage study on the population of Wales using primary and secondary care data within the Secure Anonymised Information Linkage (SAIL) Databank.

Method

Monthly rates of new diagnosis between 2000 and 2021 are presented for each long-term condition. Incidence rates post-2020 were compared with expected rates predicted using time series modelling of pre-2020 trends. The proportion of annual incidence is presented by sociodemographic factors: age, sex, social deprivation, ethnicity, frailty, and learning disability.

Results

A total of 5 476 012 diagnoses from 2 257 992 individuals are included. Incidence rates from 2020 to 2021 were lower than mean expected rates across all conditions. The largest relative deficit in incidence was in chronic obstructive pulmonary disease corresponding to 343 (95% confidence interval = 230 to 456) undiagnosed patients per 100 000 population, followed by depression, type 2 diabetes, hypertension, anxiety disorders, and asthma. A GP practice of 10 000 patients might have over 400 undiagnosed long-term conditions. No notable differences between sociodemographic profiles of post- and pre-2020 incidences were observed.

Conclusion

There is a potential backlog of undiagnosed patients with multiple long-term conditions. Resources are required to tackle anticipated workload as part of COVID-19 recovery, particularly in primary care.",,doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render; pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf +36935397,https://doi.org/10.1093/bjs/znad055,Validating a novel natural language processing pathway for automated quality assurance in surgical oncology: incomplete excision rates of 34 955 basal cell carcinomas.,"Ali SR, Dobbs TD, Jovic M, Strafford H, Fonferko-Shadrach B, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.",,The British journal of surgery,2023,2023-08-01,Y,,,,,,doi:https://doi.org/10.1093/bjs/znad055; html:https://europepmc.org/articles/PMC10416688; pdf:https://europepmc.org/articles/PMC10416688?pdf=render; pdf:https://academic.oup.com/bjs/advance-article-pdf/doi/10.1093/bjs/znad055/49561408/znad055.pdf 35079022,https://doi.org/10.1038/s41467-022-28157-3,Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.,"Konstantinoudis G, Cameletti M, Gómez-Rubio V, Gómez IL, Pirani M, Baio G, Larrauri A, Riou J, Egger M, Vineis P, Blangiardo M.",,Nature communications,2022,2022-01-25,Y,,,,"The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.",,doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render 35685390,https://doi.org/10.1016/s2666-7568(22)00072-1,"Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.","Bountziouka V, Musicha C, Allara E, Kaptoge S, Wang Q, Angelantonio ED, Butterworth AS, Thompson JR, Danesh JN, Wood AM, Nelson CP, Codd V, Samani NJ.",,The lancet. Healthy longevity,2022,2022-05-01,Y,,,,"

Background

Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences.

Methods

In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL.

Findings

422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10-4) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL.

Interpretation

Although several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit.

Funding

UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.",,doi:https://doi.org/10.1016/S2666-7568(22)00072-1; html:https://europepmc.org/articles/PMC9068584 31315158,https://doi.org/10.1002/cnm.3235,Non-invasive coronary CT angiography-derived fractional flow reserve: A benchmark study comparing the diagnostic performance of four different computational methodologies.,"Carson JM, Pant S, Roobottom C, Alcock R, Javier Blanco P, Alberto Bulant C, Vassilevski Y, Simakov S, Gamilov T, Pryamonosov R, Liang F, Ge X, Liu Y, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-08-16,Y,Fractional Flow Reserve; Benchmark; Haemodynamic Models,,,"Non-invasive coronary computed tomography (CT) angiography-derived fractional flow reserve (cFFR) is an emergent approach to determine the functional relevance of obstructive coronary lesions. Its feasibility and diagnostic performance has been reported in several studies. It is unclear if differences in sensitivity and specificity between these studies are due to study design, population, or ""computational methodology."" We evaluate the diagnostic performance of four different computational workflows for the prediction of cFFR using a limited data set of 10 patients, three based on reduced-order modelling and one based on a 3D rigid-wall model. The results for three of these methodologies yield similar accuracy of 6.5% to 10.5% mean absolute difference between computed and measured FFR. The main aspects of modelling which affected cFFR estimation were choice of inlet and outlet boundary conditions and estimation of flow distribution in the coronary network. One of the reduced-order models showed the lowest overall deviation from the clinical FFR measurements, indicating that reduced-order models are capable of a similar level of accuracy to a 3D model. In addition, this reduced-order model did not include a lumped pressure-drop model for a stenosis, which implies that the additional effort of isolating a stenosis and inserting a pressure-drop element in the spatial mesh may not be required for FFR estimation. The present benchmark study is the first of this kind, in which we attempt to homogenize the data required to compute FFR using mathematical models. The clinical data utilised in the cFFR workflows are made publicly available online.","Retrospective case series of 10 patients having coronary angiogram and invasive fractional flow reserve measurement. The authors used 4 different techniques to estimate coronary vessel flow rate and compared their measurement agreement with clinical FFA measurements and with each other. They found that all 4 methods gave different results, but one approach was more similar with the clinical gold standard. They propose this method with most worthy of further investigaiton.",doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?pdf=render 36806317,https://doi.org/10.1038/s41746-023-00749-3,Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.,"Zhang Y, Pratap A, Folarin AA, Sun S, Cummins N, Matcham F, Vairavan S, Dineley J, Ranjan Y, Rashid Z, Conde P, Stewart C, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Rambla CH, Simblett S, Nica R, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Annas P, Narayan VA, Hotopf M, Dobson RJB, RADAR-CNS consortium.",,NPJ digital medicine,2023,2023-02-17,Y,,,,"Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.",,doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render; pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf 35074819,https://doi.org/10.1136/bmjopen-2021-054414,Mapping multimorbidity in individuals with schizophrenia and bipolar disorders: evidence from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) case register.,"Bendayan R, Kraljevic Z, Shaari S, Das-Munshi J, Leipold L, Chaturvedi J, Mirza L, Aldelemi S, Searle T, Chance N, Mascio A, Skiada N, Wang T, Roberts A, Stewart R, Bean D, Dobson R.",,BMJ open,2022,2022-01-24,Y,Psychiatry; Mental health; epidemiology; Public Health; Health Informatics,,,"

Objectives

The first aim of this study was to design and develop a valid and replicable strategy to extract physical health conditions from clinical notes which are common in mental health services. Then, we examined the prevalence of these conditions in individuals with severe mental illness (SMI) and compared their individual and combined prevalence in individuals with bipolar (BD) and schizophrenia spectrum disorders (SSD).

Design

Observational study.

Setting

Secondary mental healthcare services from South London PARTICIPANTS: Our maximal sample comprised 17 500 individuals aged 15 years or older who had received a primary or secondary SMI diagnosis (International Classification of Diseases, 10th edition, F20-31) between 2007 and 2018.

Measures

We designed and implemented a data extraction strategy for 21 common physical comorbidities using a natural language processing pipeline, MedCAT. Associations were investigated with sex, age at SMI diagnosis, ethnicity and social deprivation for the whole cohort and the BD and SSD subgroups. Linear regression models were used to examine associations with disability measured by the Health of Nations Outcome Scale.

Results

Physical health data were extracted, achieving precision rates (F1) above 0.90 for all conditions. The 10 most prevalent conditions were diabetes, hypertension, asthma, arthritis, epilepsy, cerebrovascular accident, eczema, migraine, ischaemic heart disease and chronic obstructive pulmonary disease. The most prevalent combination in this population included diabetes, hypertension and asthma, regardless of their SMI diagnoses.

Conclusions

Our data extraction strategy was found to be adequate to extract physical health data from clinical notes, which is essential for future multimorbidity research using text records. We found that around 40% of our cohort had multimorbidity from which 20% had complex multimorbidity (two or more physical conditions besides SMI). Sex, age, ethnicity and social deprivation were found to be key to understand their heterogeneity and their differential contribution to disability levels in this population. These outputs have direct implications for researchers and clinicians.",,doi:https://doi.org/10.1136/bmjopen-2021-054414; html:https://europepmc.org/articles/PMC8788233; pdf:https://europepmc.org/articles/PMC8788233?pdf=render -37042240,https://doi.org/10.1161/circimaging.122.014519,Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.,"Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.",,Circulation. Cardiovascular imaging,2023,2023-04-12,N,Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques,,,"Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.",,doi:https://doi.org/10.1161/CIRCIMAGING.122.014519 36764720,https://doi.org/10.1136/bmjopen-2022-063836,"Weighting of risk factors for low birth weight: a linked routine data cohort study in Wales, UK.","Bandyopadhyay A, Jones H, Parker M, Marchant E, Evans J, Todd C, Rahman MA, Healy J, Win TL, Rowe B, Moore S, Jones A, Brophy S.",,BMJ open,2023,2023-02-10,Y,epidemiology; Public Health; Statistics & Research Methods,,,"

Objective

Globally, 20 million children are born with a birth weight below 2500 g every year, which is considered as a low birthweight (LBW) baby. This study investigates the contribution of modifiable risk factors in a nationally representative Welsh e-cohort of children and their mothers to inform opportunities to reduce LBW prevalence.

Design

A longitudinal cohort study based on anonymously linked, routinely collected multiple administrative data sets.

Participants

The cohort, (N=693 377) comprising of children born between 1 January 1998 and 31 December 2018 in Wales, was selected from the National Community Child Health Database.

Outcome measures

The risk factors associated with a binary LBW (outcome) variable were investigated with multivariable logistic regression (MLR) and decision tree (DT) models.

Results

The MLR model showed that non-singleton children had the highest risk of LBW (adjusted OR 21.74 (95% CI 21.09 to 22.40)), followed by pregnancy interval less than 1 year (2.92 (95% CI 2.70 to 3.15)), maternal physical and mental health conditions including diabetes (2.03 (1.81 to 2.28)), anaemia (1.26 (95% CI 1.16 to 1.36)), depression (1.58 (95% CI 1.43 to 1.75)), serious mental illness (1.46 (95% CI 1.04 to 2.05)), anxiety (1.22 (95% CI 1.08 to 1.38)) and use of antidepressant medication during pregnancy (1.92 (95% CI 1.20 to 3.07)). Additional maternal risk factors include smoking (1.80 (95% CI 1.76 to 1.84)), alcohol-related hospital admission (1.60 (95% CI 1.30 to 1.97)), substance misuse (1.35 (95% CI 1.29 to 1.41)) and evidence of domestic abuse (1.98 (95% CI 1.39 to 2.81)). Living in less deprived area has lower risk of LBW (0.70 (95% CI 0.67 to 0.72)). The most important risk factors from the DT models include maternal factors such as smoking, maternal weight, substance misuse record, maternal age along with deprivation-Welsh Index of Multiple Deprivation score, pregnancy interval and birth order of the child.

Conclusion

Resources to reduce the prevalence of LBW should focus on improving maternal health, reducing preterm births, increasing awareness of what is a sufficient pregnancy interval, and to provide adequate support for mothers' mental health and well-being.",,doi:https://doi.org/10.1136/bmjopen-2022-063836; html:https://europepmc.org/articles/PMC9923297; pdf:https://europepmc.org/articles/PMC9923297?pdf=render -34353320,https://doi.org/10.1186/s12916-021-02045-x,Adverse childhood experiences and child mental health: an electronic birth cohort study.,"Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.",,BMC medicine,2021,2021-08-06,Y,Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences,,,"

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.",,doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render +37042240,https://doi.org/10.1161/circimaging.122.014519,Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.,"Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.",,Circulation. Cardiovascular imaging,2023,2023-04-12,N,Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques,,,"Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.",,doi:https://doi.org/10.1161/CIRCIMAGING.122.014519 30950797,https://doi.org/10.2196/12286,Applications of Machine Learning in Real-Life Digital Health Interventions: Review of the Literature.,"Triantafyllidis AK, Tsanas A.",,Journal of medical Internet research,2019,2019-04-05,Y,Artificial intelligence; Review; data mining; Telemedicine; Machine Learning; Digital Health,Applied Analytics,,"

Background

Machine learning has attracted considerable research interest toward developing smart digital health interventions. These interventions have the potential to revolutionize health care and lead to substantial outcomes for patients and medical professionals.

Objective

Our objective was to review the literature on applications of machine learning in real-life digital health interventions, aiming to improve the understanding of researchers, clinicians, engineers, and policy makers in developing robust and impactful data-driven interventions in the health care domain.

Methods

We searched the PubMed and Scopus bibliographic databases with terms related to machine learning, to identify real-life studies of digital health interventions incorporating machine learning algorithms. We grouped those interventions according to their target (ie, target condition), study design, number of enrolled participants, follow-up duration, primary outcome and whether this had been statistically significant, machine learning algorithms used in the intervention, and outcome of the algorithms (eg, prediction).

Results

Our literature search identified 8 interventions incorporating machine learning in a real-life research setting, of which 3 (37%) were evaluated in a randomized controlled trial and 5 (63%) in a pilot or experimental single-group study. The interventions targeted depression prediction and management, speech recognition for people with speech disabilities, self-efficacy for weight loss, detection of changes in biopsychosocial condition of patients with multiple morbidity, stress management, treatment of phantom limb pain, smoking cessation, and personalized nutrition based on glycemic response. The average number of enrolled participants in the studies was 71 (range 8-214), and the average follow-up study duration was 69 days (range 3-180). Of the 8 interventions, 6 (75%) showed statistical significance (at the P=.05 level) in health outcomes.

Conclusions

This review found that digital health interventions incorporating machine learning algorithms in real-life studies can be useful and effective. Given the low number of studies identified in this review and that they did not follow a rigorous machine learning evaluation methodology, we urge the research community to conduct further studies in intervention settings following evaluation principles and demonstrating the potential of machine learning in clinical practice.",,doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205 +34353320,https://doi.org/10.1186/s12916-021-02045-x,Adverse childhood experiences and child mental health: an electronic birth cohort study.,"Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.",,BMC medicine,2021,2021-08-06,Y,Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences,,,"

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.",,doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render 36918541,https://doi.org/10.1038/s41467-023-36997-w,Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.,"Young WJ, Haessler J, Benjamins JW, Repetto L, Yao J, Isaacs A, Harper AR, Ramirez J, Garnier S, van Duijvenboden S, Baldassari AR, Concas MP, Duong T, Foco L, Isaksen JL, Mei H, Noordam R, Nursyifa C, Richmond A, Santolalla ML, Sitlani CM, Soroush N, Thériault S, Trompet S, Aeschbacher S, Ahmadizar F, Alonso A, Brody JA, Campbell A, Correa A, Darbar D, De Luca A, Deleuze JF, Ellervik C, Fuchsberger C, Goel A, Grace C, Guo X, Hansen T, Heckbert SR, Jackson RD, Kors JA, Lima-Costa MF, Linneberg A, Macfarlane PW, Morrison AC, Navarro P, Porteous DJ, Pramstaller PP, Reiner AP, Risch L, Schotten U, Shen X, Sinagra G, Soliman EZ, Stoll M, Tarazona-Santos E, Tinker A, Trajanoska K, Villard E, Warren HR, Whitsel EA, Wiggins KL, Arking DE, Avery CL, Conen D, Girotto G, Grarup N, Hayward C, Jukema JW, Mook-Kanamori DO, Olesen MS, Padmanabhan S, Psaty BM, Pattaro C, Ribeiro ALP, Rotter JI, Stricker BH, van der Harst P, van Duijn CM, Verweij N, Wilson JG, Orini M, Charron P, Watkins H, Kooperberg C, Lin HJ, Wilson JF, Kanters JK, Sotoodehnia N, Mifsud B, Lambiase PD, Tereshchenko LG, Munroe PB.",,Nature communications,2023,2023-03-14,Y,,,,"The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.",,doi:https://doi.org/10.1038/s41467-023-36997-w; html:https://europepmc.org/articles/PMC10015012; pdf:https://europepmc.org/articles/PMC10015012?pdf=render 36748660,https://doi.org/10.1111/head.14465,Depression and anxiety in women with idiopathic intracranial hypertension compared to migraine: A matched controlled cohort study.,"Mollan SP, Subramanian A, Perrins M, Nirantharakumar K, Adderley NJ, Sinclair AJ.",,Headache,2023,2023-02-07,N,Depression; Migraine; Anxiety; epidemiology; Primary Care; Idiopathic Intracranial Hypertension,,,"

Objective

To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls.

Background

Depression and anxiety are recognized comorbid conditions in those with IIH and lead to worse predicted medical outcomes. The mental health burden in IIH has not been previously evaluated in a large, matched cohort study.

Methods

We performed a population-based matched, retrospective cohort study to explore mental health outcomes (depression and anxiety). We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls).

Results

A total of 3411 women with IIH, 30,879 migraine controls and 33,495 population controls were included. Of these, 237, 2372 and 1695 women with IIH, migraine controls and population controls, respectively, developed depression during follow-up, and 179, 1826 and 1197, respectively, developed anxiety. There was a greater hazard of depression and anxiety in IIH compared to population controls (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.20-1.58; and aHR 1.40, 95% CI 1.19-1.64, respectively), while hazards were similar to migraine controls (aHR 0.98, 95% CI 0.86-1.13; and aHR 0.98, 95% CI 0.83-1.14, respectively).

Conclusion

Depression and anxiety burden in women with IIH is higher than in the general population, and comparable to that in matched women with migraine. This may indicate that presence of headache is a potential driver for comorbid depression and anxiety in IIH.",,doi:https://doi.org/10.1111/head.14465 32516805,https://doi.org/10.1093/eurheartj/ehaa375,Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.,"Hung J, Roos A, Kadesjö E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ.",,European heart journal,2021,2021-07-01,Y,Troponin; Grace; Type 2 Myocardial Infarction; High-sensitivity; Universal Definition; Type 1 Myocardial Infarction,,,"

Aims

The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.

Methods and results

In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively).

Conclusion

The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.

Trial registration

ClinicalTrials.gov number, NCT01852123.",,doi:https://doi.org/10.1093/eurheartj/ehaa375; html:https://europepmc.org/articles/PMC8266602; pdf:https://europepmc.org/articles/PMC8266602?pdf=render @@ -622,30 +623,32 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 33446033,https://doi.org/10.1177/1460458220977579,Identifying strategies to overcome roadblocks to utilising near real-time healthcare and administrative data to create a Scotland-wide learning health system.,"Mukherjee M, Cresswell K, Sheikh A.",,Health informatics journal,2021,2021-01-01,N,Qualitative Research; Governance; Electronic Health Records; Health Data; Learning Health System,,,"Creating a learning health system could help reduce variations in quality of care. Success is dependent on timely access to health data. To explore the barriers and facilitators to timely access to patients' data, we conducted in-depth semi-structured interviews with 37 purposively sampled participants from government, the NHS and academia across Scotland. Interviews were analysed using the framework approach. Participants were of the view that Scotland could play a leading role in the exploitation of routine data to drive forward service improvements, but highlighted major impediments: (i) persistence of paper-based records and a variety of information systems; (ii) the need for a proportionate approach to managing information governance; and (iii) the need for support structures to facilitate accrual, processing, linking, analysis and timely use and reuse of data for patient benefit. There is a pressing need to digitise and integrate existing health information infrastructures, guided by a nationwide proportionate information governance approach and the need to enhance technological and human capabilities to support these efforts.",,doi:https://doi.org/10.1177/1460458220977579 35290719,https://doi.org/10.1002/alz.12635,"Incidence, morbidity, mortality and disparities in dementia: A population linked electronic health records study of 4.3 million individuals.","Chung SC, Providencia R, Sofat R, Pujades-Rodriguez M, Torralbo A, Fatemifar G, Fitzpatrick NK, Taylor J, Li K, Dale C, Rossor M, Acosta-Mena D, Whittaker J, Denaxas S.",,Alzheimer's & dementia : the journal of the Alzheimer's Association,2023,2022-03-15,Y,Mortality; Alzheimer's disease; Vascular dementia; Cause of death; Dementia; epidemiology; incidence; United Kingdom; Health Inequality; Comorbidity; Electronic Health Records; Hospitalizations; Health-care Use,,,"

Introduction

We report dementia incidence, comorbidities, reasons for health-care visits, mortality, causes of death, and examined dementia patterns by relative deprivation in the UK.

Method

A longitudinal cohort analysis of linked electronic health records from 4.3 million people in the UK was conducted to investigate dementia incidence and mortality. Reasons for hospitalization and causes of death were compared in individuals with and without dementia.

Results

From 1998 to 2016 we observed 145,319 (3.1%) individuals with incident dementia. Repeated hospitalizations among senior adults for infection, unknown morbidity, and multiple primary care visits for chronic pain were observed prior to dementia diagnosis. Multiple long-term conditions are present in half of the individuals at the time of diagnosis. Individuals living in high deprivation areas had higher dementia incidence and high fatality.

Discussion

There is a considerable disparity of dementia that informs priorities of prevention and provision of patient care.",,doi:https://doi.org/10.1002/alz.12635; html:https://europepmc.org/articles/PMC10078672; pdf:https://europepmc.org/articles/PMC10078672?pdf=render 35945198,https://doi.org/10.1038/s41467-022-32095-5,Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.,"Huang QQ, Sallah N, Dunca D, Trivedi B, Hunt KA, Hodgson S, Lambert SA, Arciero E, Wright J, Griffiths C, Trembath RC, Hemingway H, Inouye M, Finer S, van Heel DA, Lumbers RT, Martin HC, Kuchenbaecker K.",,Nature communications,2022,2022-08-09,Y,,,,"Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.",,doi:https://doi.org/10.1038/s41467-022-32095-5; html:https://europepmc.org/articles/PMC9363492; pdf:https://europepmc.org/articles/PMC9363492?pdf=render; pdf:https://www.nature.com/articles/s41467-022-32095-5.pdf -35976089,https://doi.org/10.1515/cclm-2022-0135,"Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort.","Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, Mills NL, O'Rahilly S, Sattar N.",,Clinical chemistry and laboratory medicine,2022,2022-08-18,N,Biochemical markers; Guidelines; Reference Ranges,,,"

Objectives

Growth differentiation factor (GDF)-15 is attracting interest as a biomarker in several areas of medicine. We aimed to evaluate the reference range for GDF-15 in a general population, and to explore demographics, classical cardiovascular disease risk factors, and other cardiac biomarkers associated with GDF-15.

Methods

GDF-15 was measured in serum from 19,462 individuals in the Generation Scotland Scottish Family Health Study. Associations of cardiometabolic risk factors with GDF-15 were tested using adjusted linear regression. Among 18,507 participants with no heart disease, heart failure, or stroke, and not pregnant, reference ranges (median and 97.5th centiles) were derived by decade age bands and sex.

Results

Among males in the reference range population, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135) pg/mL, rising to 931 (2,492) pg/mL at 50-59 years, and 2,152 (5,972) pg/mL at ≥80 years. In females, median GDF-15 at age <30 years was 628 (2,195) pg/mL, 881 (2,323) pg/mL at 50-59 years, and 1847 (6,830) pg/mL at ≥80 years. Among those known to be pregnant, median GDF-15 was 19,311 pg/mL. After adjustment, GDF-15 was higher in participants with adverse cardiovascular risk factors, including current smoking (+26.1%), those with previous heart disease (+12.7%), stroke (+17.1%), heart failure (+25.3%), and particularly diabetes (+60.2%). GDF-15 had positive associations with cardiac biomarkers cardiac troponin I, cardiac troponin T, and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Conclusions

These data define reference ranges for GDF-15 for comparison in future studies, and identify potentially confounding risk factors and mediators to be considered in interpreting GDF-15 concentrations.",,doi:https://doi.org/10.1515/cclm-2022-0135; html:https://europepmc.org/articles/PMC9524804; pdf:https://europepmc.org/articles/PMC9524804?pdf=render; doi:https://doi.org/10.1515/cclm-2022-0135 35786634,https://doi.org/10.2196/37821,Methodological Issues in Using a Common Data Model of COVID-19 Vaccine Uptake and Important Adverse Events of Interest: Feasibility Study of Data and Connectivity COVID-19 Vaccines Pharmacovigilance in the United Kingdom.,"Delanerolle G, Williams R, Stipancic A, Byford R, Forbes A, Tsang RSM, Anand SN, Bradley D, Murphy S, Akbari A, Bedston S, Lyons RA, Owen R, Torabi F, Beggs J, Chuter A, Balharry D, Joy M, Sheikh A, Hobbs FDR, de Lusignan S.",,JMIR formative research,2022,2022-08-22,Y,Clinical outcome; Sinus Thrombosis; Health Information; Pharmacovigilance; anaphylaxis; Vaccine Uptake; Systematized Nomenclature Of Medicine; Data Model; Medical Outcome; Health Database; Vaccine Effect; Covid-19; Covid-19 Vaccines; Clinical Coding System,,,"

Background

The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom.

Objective

This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d).

Methods

Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days.

Results

We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies.

Conclusions

This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.",,doi:https://doi.org/10.2196/37821; html:https://europepmc.org/articles/PMC9400842; pdf:https://europepmc.org/articles/PMC9400842?pdf=render +35976089,https://doi.org/10.1515/cclm-2022-0135,"Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort.","Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, Mills NL, O'Rahilly S, Sattar N.",,Clinical chemistry and laboratory medicine,2022,2022-08-18,N,Biochemical markers; Guidelines; Reference Ranges,,,"

Objectives

Growth differentiation factor (GDF)-15 is attracting interest as a biomarker in several areas of medicine. We aimed to evaluate the reference range for GDF-15 in a general population, and to explore demographics, classical cardiovascular disease risk factors, and other cardiac biomarkers associated with GDF-15.

Methods

GDF-15 was measured in serum from 19,462 individuals in the Generation Scotland Scottish Family Health Study. Associations of cardiometabolic risk factors with GDF-15 were tested using adjusted linear regression. Among 18,507 participants with no heart disease, heart failure, or stroke, and not pregnant, reference ranges (median and 97.5th centiles) were derived by decade age bands and sex.

Results

Among males in the reference range population, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135) pg/mL, rising to 931 (2,492) pg/mL at 50-59 years, and 2,152 (5,972) pg/mL at ≥80 years. In females, median GDF-15 at age <30 years was 628 (2,195) pg/mL, 881 (2,323) pg/mL at 50-59 years, and 1847 (6,830) pg/mL at ≥80 years. Among those known to be pregnant, median GDF-15 was 19,311 pg/mL. After adjustment, GDF-15 was higher in participants with adverse cardiovascular risk factors, including current smoking (+26.1%), those with previous heart disease (+12.7%), stroke (+17.1%), heart failure (+25.3%), and particularly diabetes (+60.2%). GDF-15 had positive associations with cardiac biomarkers cardiac troponin I, cardiac troponin T, and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Conclusions

These data define reference ranges for GDF-15 for comparison in future studies, and identify potentially confounding risk factors and mediators to be considered in interpreting GDF-15 concentrations.",,doi:https://doi.org/10.1515/cclm-2022-0135; html:https://europepmc.org/articles/PMC9524804; pdf:https://europepmc.org/articles/PMC9524804?pdf=render; doi:https://doi.org/10.1515/cclm-2022-0135 36543561,https://doi.org/10.3399/bjgp.2022.0156,Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GY, Lane DA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2022-12-21,Y,"Anticoagulants; Atrial fibrillation; Primary Health Care; Nursing Homes; Long-term Care; Practice Patterns, Physicians’",,,"

Background

Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents.

Aim

To explore factors associated with OAC prescription.

Design and setting

Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18.

Method

Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank.

Results

Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription.

Conclusion

There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.",,doi:https://doi.org/10.3399/BJGP.2022.0156; html:https://europepmc.org/articles/PMC9799341; pdf:https://europepmc.org/articles/PMC9799341?pdf=render; pdf:https://bjgp.org/content/bjgp/73/726/e43.full.pdf 32206896,https://doi.org/10.1007/s00394-020-02220-5,Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study.,"Laguzzi F, Baldassarre D, Veglia F, Strawbridge RJ, Humphries SE, Rauramaa R, Smit AJ, Giral P, Silveira A, Tremoli E, Hamsten A, de Faire U, Frumento P, Leander K, IMPROVE Study group.",,European journal of nutrition,2021,2020-03-24,Y,Atherosclerosis; epidemiology; Carotid intima-media thickness; Alcohol drinking; Progression,,,"

Background/aim

The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption.

Methods

Between 2002-2004, 1772 men and 1931 women aged 54-79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 - 5 g/d), low (> 5 to  ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women,  > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude.

Results

Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMTmean[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMTmean[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMTmean[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMTmean[- 0.009(95% - 0.016; - 0.002)] and ICA-IMTmax[- 0.016(95%: - 0.032; - 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT.

Conclusion

In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.",,doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render 36475361,https://doi.org/10.1302/2633-1462.312.bjo-2022-0130.r1,Variation in timely surgery for severe open tibial fractures by time and place of presentation in England from 2012 to 2019 : a cohort study using data collected nationally by the Trauma Audit and Research Network.,"Shah A, Judge A, Griffin XL.",,Bone & joint open,2022,2022-12-01,Y,Trauma; Sensitivity analysis; Debridement; Logistic regression; Cohort study; Orthopaedics; Injury Severity Score; Health Care Quality; Soft-tissue; Open Fracture; Tarn; Regression Analyses; Open Fractures Of The Tibia,,,"

Aims

Several studies have reported that patients presenting during the evening or weekend have poorer quality healthcare. Our objective was to examine how timely surgery for patients with severe open tibial fracture varies by day and time of presentation and by type of hospital. This cohort study included patients with severe open tibial fractures from the Trauma Audit and Research Network (TARN).

Methods

Provision of prompt surgery (debridement within 12 hours and soft-tissue coverage in 72 hours) was examined, using multivariate logistic regression to derive adjusted risk ratios (RRs). Time was categorized into three eight-hour intervals for each day of the week. The models were adjusted for treatment in a major trauma centre (MTC), sex, age, year of presentation, injury severity score, injury mechanism, and number of operations each patient received.

Results

We studied 8,258 patients from 175 hospitals. Patients presenting during the day (08:00 to 15:59; risk ratio (RR) 1.11, 95% confidence interval (CI) 1.02 to 1.20) were more likely to receive debridement within 12 hours, and patients presenting at night (16:00 to 23:59; RR 0.56, 95% CI 0.51 to 0.62) were less likely to achieve the target; triage to a MTC had no effect. Day of presentation was associated with soft-tissue coverage within 72 hours; patients presenting on a Thursday or Friday being less likely to receive this surgery within 72 hours (Thursday RR 0.88, 95% CI 0.81 to 0.97; Friday RR 0.89, 95% CI 0.81 to 0.98), and the standard less likely to be achieved for those treated in 'non-MTC' hospitals (RR 0.76, 95% CI 0.70 to 0.82).

Conclusion

Variations in care were observed for timely surgery for severe open tibial fractures with debridement surgery affected by time of presentation and soft-tissue coverage affected by day of presentation and type of hospital. The variation is unwarranted and highlights that there are opportunities to substantially improve the delivery and quality of care for patients with severe open tibial fracture.Cite this article: Bone Jt Open 2022;3(12):941-952.",,doi:https://doi.org/10.1302/2633-1462.312.BJO-2022-0130.R1; html:https://europepmc.org/articles/PMC9783273; pdf:https://europepmc.org/articles/PMC9783273?pdf=render 33711543,https://doi.org/10.1016/j.jbi.2021.103728,Explainable automated coding of clinical notes using hierarchical label-wise attention networks and label embedding initialisation.,"Dong H, Suárez-Paniagua V, Whiteley W, Wu H.",,Journal of biomedical informatics,2021,2021-03-09,N,Natural Language Processing; Multi-label Classification; Deep Learning; Attention Mechanisms; Automated Medical Coding; Explainability; Label Correlation,,,"

Background

Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlations among medical codes which can potentially be exploited to improve the performance.

Methods

To address the issues of model explainability and label correlations, we propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS (National Health Service) COVID-19 (Coronavirus disease 2019) shielding codes. Experiments were conducted to compare the HLAN model and label embedding initialisation to the state-of-the-art neural network based methods, including variants of Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs).

Results

HLAN achieved the best Micro-level AUC and F1 on the top-50 code prediction, 91.9% and 64.1%, respectively; and comparable results on the NHS COVID-19 shielding code prediction to other models: around 97% Micro-level AUC. More importantly, in the analysis of model explanations, by highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to the CNN-based models and its downgraded baselines, HAN and HA-GRU. Label embedding (LE) initialisation significantly boosted the previous state-of-the-art model, CNN with attention mechanisms, on the full code prediction to 52.5% Micro-level F1. The analysis of the layers initialised with label embeddings further explains the effect of this initialisation approach. The source code of the implementation and the results are openly available at https://github.com/acadTags/Explainable-Automated-Medical-Coding.

Conclusion

We draw the conclusion from the evaluation results and analyses. First, with hierarchical label-wise attention mechanisms, HLAN can provide better or comparable results for automated coding to the state-of-the-art, CNN-based models. Second, HLAN can provide more comprehensive explanations for each label by highlighting key words and sentences in the discharge summaries, compared to the n-grams in the CNN-based models and the downgraded baselines, HAN and HA-GRU. Third, the performance of deep learning based multi-label classification for automated coding can be consistently boosted by initialising label embeddings that captures the correlations among labels. We further discuss the advantages and drawbacks of the overall method regarding its potential to be deployed to a hospital and suggest areas for future studies.",,doi:https://doi.org/10.1016/j.jbi.2021.103728 33469151,https://doi.org/10.1038/s42003-020-01613-w,LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes.,"Herdenberg C, Mutie PM, Billing O, Abdullah A, Strawbridge RJ, Dahlman I, Tuck S, Holmlund C, Arner P, Henriksson R, Franks PW, Hedman H.",,Communications biology,2021,2021-01-19,Y,,,,"Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.",,doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render +37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statins Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys RR, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,N,,,,"

Background

There has been considerable interest in statins due to their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We employed two-sample Mendelian randomization (MR) to investigate: (1) the causal role of genetically mimic both cholesterol-dependent (via low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (via Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)) levels and MS risk and severity; and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n =7,069).

Results

The results of MR using the inverse variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway, (OR 0.86 (95% CI 0.78 to 0.95), p-value 3.80E-03) is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. MR results also show that lifelong higher HDL-C (OR 1.14 (95% CI 1.04 to1.26), p-value 7.94E-03) increase MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Conclusion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Since RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk via a cholesterol-independent pathway (i.e., RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,doi:https://doi.org/10.1212/WNL.0000000000207777 36620207,https://doi.org/10.3389/fphys.2022.1089343,Incorporating structural abnormalities in equivalent dipole layer based ECG simulations.,"Boonstra MJ, Oostendorp TF, Roudijk RW, Kloosterman M, Asselbergs FW, Loh P, Van Dam PM.",,Frontiers in physiology,2022,2022-12-22,Y,Simulation; Myocardial Disease; Electrocardiogram (Ecg); Cardiac Activation; Ecgsim; Equivalent Dipole Layer,,,"Introduction: Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study. Methods: Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping. Results: Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, p < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms. Discussion: A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.",,doi:https://doi.org/10.3389/fphys.2022.1089343; html:https://europepmc.org/articles/PMC9814485; pdf:https://europepmc.org/articles/PMC9814485?pdf=render -34298561,https://doi.org/10.1177/2047487320914115,Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.,"Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, Gravenor M, Halcox J.",,European journal of preventive cardiology,2021,2021-07-01,N,Lipids; Cholesterol; Percutaneous coronary intervention; Secondary Prevention; Pharmacoepidemiology; statins,,,"

Aims

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients.

Methods

We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge.

Results

Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target.

Conclusion

There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.",,doi:https://doi.org/10.1177/2047487320914115 34765951,https://doi.org/10.1016/j.eclinm.2021.101163,Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.,"Staplin N, Roddick AJ, Emberson J, Reith C, Riding A, Wonnacott A, Kuverji A, Bhandari S, Baigent C, Haynes R, Herrington WG.",,EClinicalMedicine,2021,2021-10-26,Y,Safety; Heart Failure; Randomized Trials; Ckd; Sodium-glucose Co-transporter 2 Inhibitors,,,"

Background

The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.

Methods

We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468).

Findings

Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS).

Interpretations

The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date.

Funding

MRC-UK & KRUK.",,doi:https://doi.org/10.1016/j.eclinm.2021.101163; html:https://europepmc.org/articles/PMC8571171; pdf:https://europepmc.org/articles/PMC8571171?pdf=render +34298561,https://doi.org/10.1177/2047487320914115,Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.,"Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, Gravenor M, Halcox J.",,European journal of preventive cardiology,2021,2021-07-01,N,Lipids; Cholesterol; Percutaneous coronary intervention; Secondary Prevention; Pharmacoepidemiology; statins,,,"

Aims

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients.

Methods

We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge.

Results

Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target.

Conclusion

There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.",,doi:https://doi.org/10.1177/2047487320914115 +37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,Y,Depression; Mobile phone; Missing Data; Smartphones; Mobile Health; Wearable Devices; Behavioral Patterns; Digital Phenotypes,,,"

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088; pdf:https://www.jmir.org/2023/1/e45233/PDF 37156273,https://doi.org/10.1016/j.jad.2023.04.138,Subjective and objective sleep and circadian parameters as predictors of depression-related outcomes: A machine learning approach in UK Biobank.,"Lyall LM, Sangha N, Zhu X, Lyall DM, Ward J, Strawbridge RJ, Cullen B, Smith DJ.",,Journal of affective disorders,2023,2023-05-06,N,Sleep; Depression; Circadian rhythms; Postnatal Depression; Inactivity; Rest-activity,,,"

Background

Sleep and circadian disruption are associated with depression onset and severity, but it is unclear which features (e.g., sleep duration, chronotype) are important and whether they can identify individuals showing poorer outcomes.

Methods

Within a subset of the UK Biobank with actigraphy and mental health data (n = 64,353), penalised regression identified the most useful of 51 sleep/rest-activity predictors of depression-related outcomes; including case-control (Major Depression (MD) vs. controls; postnatal depression vs. controls) and within-case comparisons (severe vs. moderate MD; early vs. later onset, atypical vs. typical symptoms; comorbid anxiety; suicidality). Best models (of lasso, ridge, and elastic net) were selected based on Area Under the Curve (AUC).

Results

For MD vs. controls (n(MD) = 24,229; n(control) = 40,124), lasso AUC was 0.68, 95 % confidence interval (CI) 0.67-0.69. Discrimination was reasonable for atypical vs. typical symptoms (n(atypical) = 958; n(typical) = 18,722; ridge: AUC 0.74, 95 % CI 0.71-0.77) but poor for remaining models (AUCs 0.59-0.67). Key predictors across most models included: difficulty getting up, insomnia symptoms, snoring, actigraphy-measured daytime inactivity and lower morning activity (~8 am). In a distinct subset (n = 310,718), the number of these factors shown was associated with all depression outcomes.

Limitations

Analyses were cross-sectional and in middle-/older aged adults: comparison with longitudinal investigations and younger cohorts is necessary.

Discussion

Sleep and circadian measures alone provided poor to moderate discrimination of depression outcomes, but several characteristics were identified that may be clinically useful. Future work should assess these features alongside broader sociodemographic, lifestyle and genetic features.",,doi:https://doi.org/10.1016/j.jad.2023.04.138 34508578,https://doi.org/10.1093/gigascience/giab059,Desiderata for the development of next-generation electronic health record phenotype libraries.,"Chapman M, Mumtaz S, Rasmussen LV, Karwath A, Gkoutos GV, Gao C, Thayer D, Pacheco JA, Parkinson H, Richesson RL, Jefferson E, Denaxas S, Curcin V.",,GigaScience,2021,2021-09-01,Y,Electronic Health Records; Computable Phenotype; Ehr-based Phenotyping; Phenotype Library,,,"

Background

High-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In this work, we present a set of desiderata for the design of a next-generation phenotype library that is able to ensure the quality of hosted definitions by combining the functionality currently offered by disparate tooling.

Methods

A group of researchers examined work to date on phenotype models, implementation, and validation, as well as contemporary phenotype libraries developed as a part of their own phenomics communities. Existing phenotype frameworks were also examined. This work was translated and refined by all the authors into a set of best practices.

Results

We present 14 library desiderata that promote high-quality phenotype definitions, in the areas of modelling, logging, validation, and sharing and warehousing.

Conclusions

There are a number of choices to be made when constructing phenotype libraries. Our considerations distil the best practices in the field and include pointers towards their further development to support portable, reproducible, and clinically valid phenotype design. The provision of high-quality phenotype definitions enables electronic health record data to be more effectively used in medical domains.",,doi:https://doi.org/10.1093/gigascience/giab059; html:https://europepmc.org/articles/PMC8434766; pdf:https://europepmc.org/articles/PMC8434766?pdf=render 33436761,https://doi.org/10.1038/s41598-020-79964-x,The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals.,"Strawbridge RJ, Johnston KJA, Bailey MES, Baldassarre D, Cullen B, Eriksson P, deFaire U, Ferguson A, Gigante B, Giral P, Graham N, Hamsten A, Humphries SE, Kurl S, Lyall DM, Lyall LM, Pell JP, Pirro M, Savonen K, Smit AJ, Tremoli E, Tomainen TP, Veglia F, Ward J, Sennblad B, Smith DJ.",,Scientific reports,2021,2021-01-12,Y,,,,"Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.",,doi:https://doi.org/10.1038/s41598-020-79964-x; html:https://europepmc.org/articles/PMC7804422; pdf:https://europepmc.org/articles/PMC7804422?pdf=render 32641105,https://doi.org/10.1186/s12874-020-01025-8,Multivariate network meta-analysis incorporating class effects.,"Owen RK, Bujkiewicz S, Tincello DG, Abrams KR.",,BMC medical research methodology,2020,2020-07-08,Y,Meta-analysis; Multivariate; Class Effect; Network Meta-analysis; Mixed Treatment Comparisons,,,"

Background

Network meta-analysis synthesises data from a number of clinical trials in order to assess the comparative efficacy of multiple healthcare interventions in similar patient populations. In situations where clinical trial data are heterogeneously reported i.e. data are missing for one or more outcomes of interest, synthesising such data can lead to disconnected networks of evidence, increased uncertainty, and potentially biased estimates which can have severe implications for decision-making. To overcome this issue, strength can be borrowed between outcomes of interest in multivariate network meta-analyses. Furthermore, in situations where there are relatively few trials informing each treatment comparison, there is a potential issue with the sparsity of data in the treatment networks, which can lead to substantial parameter uncertainty. A multivariate network meta-analysis approach can be further extended to borrow strength between interventions of the same class using hierarchical models.

Methods

We extend the trivariate network meta-analysis model to incorporate the exchangeability between treatment effects belonging to the same class of intervention to increase precision in treatment effect estimates. We further incorporate a missing data framework to estimate uncertainty in trials that did not report measures of variability in order to maximise the use of all available information for healthcare decision-making. The methods are applied to a motivating dataset in overactive bladder syndrome. The outcomes of interest were mean change from baseline in incontinence, voiding and urgency episodes. All models were fitted using Bayesian Markov Chain Monte Carlo (MCMC) methods in WinBUGS.

Results

All models (univariate, multivariate, and multivariate models incorporating class effects) produced similar point estimates for all treatment effects. Incorporating class effects in multivariate models often increased precision in treatment effect estimates.

Conclusions

Multivariate network meta-analysis incorporating class effects allowed for the comparison of all interventions across all outcome measures to ameliorate the potential impact of outcome reporting bias, and further borrowed strength between interventions belonging to the same class of treatment to increase the precision in treatment effect estimates for healthcare policy and decision-making.",,doi:https://doi.org/10.1186/s12874-020-01025-8; html:https://europepmc.org/articles/PMC7341581; pdf:https://europepmc.org/articles/PMC7341581?pdf=render 31845899,https://doi.org/10.2196/14782,Efficient Reuse of Natural Language Processing Models for Phenotype-Mention Identification in Free-text Electronic Medical Records: A Phenotype Embedding Approach.,"Wu H, Hodgson K, Dyson S, Morley KI, Ibrahim ZM, Iqbal E, Stewart R, Dobson RJ, Sudlow C.",,JMIR medical informatics,2019,2019-12-17,Y,Phenotype; Clustering; Machine Learning; Electronic Health Records; Natural Language Processing; Text Mining; Word Embedding; Model Adaptation; Phenotype Embedding,Applied Analytics,,"

Background

Much effort has been put into the use of automated approaches, such as natural language processing (NLP), to mine or extract data from free-text medical records in order to construct comprehensive patient profiles for delivering better health care. Reusing NLP models in new settings, however, remains cumbersome, as it requires validation and retraining on new data iteratively to achieve convergent results.

Objective

The aim of this work is to minimize the effort involved in reusing NLP models on free-text medical records.

Methods

We formally define and analyze the model adaptation problem in phenotype-mention identification tasks. We identify ""duplicate waste"" and ""imbalance waste,"" which collectively impede efficient model reuse. We propose a phenotype embedding-based approach to minimize these sources of waste without the need for labelled data from new settings.

Results

We conduct experiments on data from a large mental health registry to reuse NLP models in four phenotype-mention identification tasks. The proposed approach can choose the best model for a new task, identifying up to 76% waste (duplicate waste), that is, phenotype mentions without the need for validation and model retraining and with very good performance (93%-97% accuracy). It can also provide guidance for validating and retraining the selected model for novel language patterns in new tasks, saving around 80% waste (imbalance waste), that is, the effort required in ""blind"" model-adaptation approaches.

Conclusions

Adapting pretrained NLP models for new tasks can be more efficient and effective if the language pattern landscapes of old settings and new settings can be made explicit and comparable. Our experiments show that the phenotype-mention embedding approach is an effective way to model language patterns for phenotype-mention identification tasks and that its use can guide efficient NLP model reuse.",Wu et el. developed a computer algorithm which can transform clinical letters into databases for research. Their approach in processing information in clinical letters is more flexible compared to those before allowing users to define concepts which they want to find in the letters. ,doi:https://doi.org/10.2196/14782; html:https://europepmc.org/articles/PMC6938594 33123364,https://doi.org/10.1093/ckj/sfaa192,Temporal changes in complement activation in haemodialysis patients with COVID-19 as a predictor of disease progression.,"Prendecki M, Clarke C, Medjeral-Thomas N, McAdoo SP, Sandhu E, Peters JE, Thomas DC, Willicombe M, Botto M, Pickering MC.",,Clinical kidney journal,2020,2020-10-02,Y,Complement; Haemodialysis; Covid-19,,,"

Background

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

Methods

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

Results

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

Conclusions

Our findings suggest that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage. C5a may be an earlier biomarker of disease severity than conventional parameters such as C-reactive protein and this warrants further investigation in dedicated biomarker studies. Our data support the testing of complement inhibition as a therapeutic strategy for patients with severe COVID-19.",,doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render -36715329,https://doi.org/10.1093/bjd/ljac090,"The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.","Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.",,The British journal of dermatology,2023,2023-02-01,N,,,,"

Background

Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.

Objectives

To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.

Methods

The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.

Results

A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million.

Conclusions

Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.",,doi:https://doi.org/10.1093/bjd/ljac090 31857590,https://doi.org/10.1038/s41597-019-0337-6,Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction.,"Bravo-Merodio L, Acharjee A, Hazeldine J, Bentley C, Foster M, Gkoutos GV, Lord JM.",,Scientific data,2019,2019-12-19,Y,,,,"The immune response to major trauma has been analysed mainly within post-hospital admission settings where the inflammatory response is already underway and the early drivers of clinical outcome cannot be readily determined. Thus, there is a need to better understand the immediate immune response to injury and how this might influence important patient outcomes such as multi-organ dysfunction syndrome (MODS). In this study, we have assessed the immune response to trauma in 61 patients at three different post-injury time points (ultra-early (<=1 h), 4-12 h, 48-72 h) and analysed relationships with the development of MODS. We developed a pipeline using Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods that were able to identify 3 physiological features (decrease in neutrophil CD62L and CD63 expression and monocyte CD63 expression and frequency) as possible biomarkers for MODS development. After univariate and multivariate analysis for each feature alongside a stability analysis, the addition of these 3 markers to standard clinical trauma injury severity scores yields a Generalized Liner Model (GLM) with an average Area Under the Curve value of 0.92 ± 0.06. This performance provides an 8% improvement over the Probability of Survival (PS14) outcome measure and a 13% improvement over the New Injury Severity Score (NISS) for identifying patients at risk of MODS.",,doi:https://doi.org/10.1038/s41597-019-0337-6; html:https://europepmc.org/articles/PMC6923383; pdf:https://europepmc.org/articles/PMC6923383?pdf=render +36715329,https://doi.org/10.1093/bjd/ljac090,"The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.","Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.",,The British journal of dermatology,2023,2023-02-01,N,,,,"

Background

Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.

Objectives

To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.

Methods

The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.

Results

A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million.

Conclusions

Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.",,doi:https://doi.org/10.1093/bjd/ljac090 34824100,https://doi.org/10.1136/openhrt-2021-001769,Implementation of an early rule-out pathway for myocardial infarction using a high-sensitivity cardiac troponin T assay.,"Sandeman D, Syed MBJ, Kimenai DM, Lee KK, Anand A, Joshi SS, Dinnel L, Wenham PR, Campbell K, Jarvie M, Galloway D, Anderson M, Roy B, Andrews JPM, Strachan FE, Ferry AV, Chapman AR, Elsby S, Francis M, Cargill R, Shah ASV, Mills NL.",,Open heart,2021,2021-11-01,Y,Biomarkers; Chest pain; acute coronary syndrome,,,"

Objectives

Patients with suspected acute coronary syndrome and high-sensitivity cardiac troponin (hs-cTn) concentrations below the limit of detection at presentation are low risk. We aim to determine whether implementing this approach facilitates the safe early discharge of patients.

Methods

In a prospective single-centre cohort study, consecutive patients with suspected acute coronary syndrome were included before (standard care) and after (intervention) implementation of an early rule-out pathway. During standard care, myocardial infarction was ruled out if hs-cTnT concentrations were <99th centile (14 ng/L) at presentation and at 6-12 hours after symptom onset. In the intervention, patients were ruled out if hs-cTnT concentrations were <5 ng/L at presentation and symptoms present for ≥3 hours or were ≥5 ng/L and unchanged within the reference range at 3 hours. We compared duration of stay (efficacy) and all-cause death at 1 year (safety) before and after implementation.

Results

We included 10 315 consecutive patients (64±16 years, 46% women) with 6642 (64%) and 3673 (36%) in the standard care and intervention groups, respectively. Duration of stay was reduced from 534 (IQR, 220-2279) to 390 (IQR, 218-1910) min (p<0.001) after implementation. At 1 year, all-cause death occurred in 10.9% (721 of 6642) and 10.4% (381 of 3673) of patients in the standard care group (referent) and intervention group, respectively (adjusted OR 1.02, 95% CI 0.88 to 1.18).

Conclusion

In patients with suspected acute coronary syndrome, implementing an early rule-out pathway using hs-cTnT concentrations <5 ng/L at presentation reduced the duration of stay in hospital without compromising safety.",,doi:https://doi.org/10.1136/openhrt-2021-001769; html:https://europepmc.org/articles/PMC8627412; pdf:https://europepmc.org/articles/PMC8627412?pdf=render 36881701,https://doi.org/10.1097/jtn.0000000000000708,Perceptions of an Interactive Trauma Recovery Information Booklet.,"Reeder SC, Ekegren CL, Mather AM, Kimmel LA, Webb MJ, Pellegrini M, Cameron PA, Gabbe BJ.",,Journal of trauma nursing : the official journal of the Society of Trauma Nurses,2023,2023-03-01,N,,,,"

Background

Previous research has shown that people with traumatic injuries have unmet information needs with respect to their injuries, management, and recovery. An interactive trauma recovery information booklet was developed and implemented to address these information needs at a major trauma center in Victoria, Australia.

Objective

The aim of this quality improvement project was to explore patient and clinician perceptions of a recovery information booklet introduced into a trauma ward.

Methods

Semistructured interviews with trauma patients, family members, and health professionals were undertaken and thematically analyzed using a framework approach. In total, 34 patients, 10 family members, and 26 health professionals were interviewed.

Results

Overall, the booklet was well accepted by most participants and was perceived to contain useful information. The design, content, pictures, and readability were all positively appraised. Many participants used the booklet to record personalized information and to ask health professionals questions about their injuries and management.

Conclusion

Our findings highlight the usefulness and acceptability of a low-cost interactive booklet intervention to facilitate the provision of quality of information and patient-health professional interactions on a trauma ward.",,doi:https://doi.org/10.1097/JTN.0000000000000708 35429382,https://doi.org/10.1093/infdis/jiac146,Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).,"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The Journal of infectious diseases,2022,2022-11-01,Y,Antibodies; Vaccination; Waning; Long-term Care Facilities; Covid-19,,,"General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242 34784292,https://doi.org/10.2196/32587,Investigating the Use of Digital Health Technology to Monitor COVID-19 and Its Effects: Protocol for an Observational Study (Covid Collab Study).,"Stewart C, Ranjan Y, Conde P, Rashid Z, Sankesara H, Bai X, Dobson RJB, Folarin AA.",,JMIR research protocols,2021,2021-12-08,Y,Monitoring; Infectious disease; Recovery; Mobile phone; Feasibility; Surveillance; Data; Mental health; Observational; Smartphone; Wearable; Mobile Health; Wearable Devices; Digital Health; Crowdsourced; Covid-19,,,"

Background

The ubiquity of mobile phones and increasing use of wearable fitness trackers offer a wide-ranging window into people's health and well-being. There are clear advantages in using remote monitoring technologies to gain an insight into health, particularly under the shadow of the COVID-19 pandemic.

Objective

Covid Collab is a crowdsourced study that was set up to investigate the feasibility of identifying, monitoring, and understanding the stratification of SARS-CoV-2 infection and recovery through remote monitoring technologies. Additionally, we will assess the impacts of the COVID-19 pandemic and associated social measures on people's behavior, physical health, and mental well-being.

Methods

Participants will remotely enroll in the study through the Mass Science app to donate historic and prospective mobile phone data, fitness tracking wearable data, and regular COVID-19-related and mental health-related survey data. The data collection period will cover a continuous period (ie, both before and after any reported infections), so that comparisons to a participant's own baseline can be made. We plan to carry out analyses in several areas, which will cover symptomatology; risk factors; the machine learning-based classification of illness; and trajectories of recovery, mental well-being, and activity.

Results

As of June 2021, there are over 17,000 participants-largely from the United Kingdom-and enrollment is ongoing.

Conclusions

This paper introduces a crowdsourced study that will include remotely enrolled participants to record mobile health data throughout the COVID-19 pandemic. The data collected may help researchers investigate a variety of areas, including COVID-19 progression; mental well-being during the pandemic; and the adherence of remote, digitally enrolled participants.

International registered report identifier (irrid)

DERR1-10.2196/32587.",,doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240 -37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 36606535,https://doi.org/10.1111/jdv.18841,The association between atopic eczema and lymphopenia: Results from a UK cohort study with replication in US survey data.,"Hollestein LM, Ye MYF, Ang KL, Forbes H, Mansfield KE, Abuabara K, Smeeth L, Langan SM.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2023,2023-01-25,N,,,,"

Background

Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia.

Objective

To determine if AE is associated with lymphopenia.

Methods

We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]).

Results

Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 109 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 109 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections.

Conclusion

Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.",,doi:https://doi.org/10.1111/jdv.18841 +37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 31971603,https://doi.org/10.2340/00015555-3384,Psoriasis and Genetics.,"Dand N, Mahil SK, Capon F, Smith CH, Simpson MA, Barker JN.",,Acta dermato-venereologica,2020,2020-01-30,Y,Genetics; Psoriasis; Treatment outcome; Disease Progression; Precision Medicine,,,"Psoriasis is a common inflammatory skin disease caused by the interplay between multiple genetic and environmental risk factors. This review summarises recent progress in elucidating the genetic basis of psoriasis, particularly through large genome-wide association studies. We illustrate the power of genetic analyses for disease stratification. Psoriasis can be stratified by phenotype (common plaque versus rare pustular variants), or by outcome (prognosis, comorbidities, response to treatment); recent progress has been made in delineating the genetic contribution in each of these areas. We also highlight how genetic data can directly inform the development of effective psoriasis treatments.",,doi:https://doi.org/10.2340/00015555-3384; html:https://europepmc.org/articles/PMC9128944; pdf:https://europepmc.org/articles/PMC9128944?pdf=render 31532828,https://doi.org/10.1210/clinem/dgz006,Increased Infection Risk in Addison's Disease and Congenital Adrenal Hyperplasia. ,"Tresoldi AS, Sumilo D, Perrins M, Toulis KA, Prete A, Reddy N, Wass JAH, Arlt W, Nirantharakumar K.",,The Journal of clinical endocrinology and metabolism,2020,2020-02-01,Y,,,,"Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown. To estimate infection risk in PAI due to Addison's disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting. Retrospective cohort study using UK data collected from 1995 to 2018. Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls. A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64-2.69], CAH 3.23 [95% CI 1.21-8.61]), UTIs (AD 1.51 [95% CI 1.29-1.77], CAH 2.20 [95% CI 1.43-3.34]), and GIIs (AD 3.80 [95% CI 2.99-4.84], CAH 1.93 [95% CI 1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69-1.77], CAH 1.77 [95% CI 1.66-1.89]) and antifungals (AD 1.89 [95% CI 1.74-2.05], CAH 1.91 [95% CI 1.50-2.43]). There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.",People who suffer with primary adrenal insufficiency are more likely to be admitted to hospital. But the risk to patients catching infections whilst being treated in hospital is unknown. This study found that people with PAI being treated in hospital have a higher risk of catching an infection. Some of this risk is linked with how PAI is treated.,doi:https://doi.org/10.1210/clinem/dgz006; html:https://europepmc.org/articles/PMC7046014 36382153,https://doi.org/10.5334/gh.1166,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.,"Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.",,Global heart,2022,2022-10-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors,,,Highlights  Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.,,doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render @@ -664,15 +667,15 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 35032176,https://doi.org/10.1007/s00125-021-05640-y,Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings.,"Dziopa K, Asselbergs FW, Gratton J, Chaturvedi N, Schmidt AF.",,Diabetologia,2022,2022-01-15,Y,Prediction; Diabetes; Cardiovascular disease; Risk Score,,,"

Aims/hypothesis

We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes.

Methods

Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation.

Results

We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001).

Conclusions/interpretation

CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability.",,doi:https://doi.org/10.1007/s00125-021-05640-y; html:https://europepmc.org/articles/PMC8894164; pdf:https://europepmc.org/articles/PMC8894164?pdf=render 36609574,https://doi.org/10.1038/s41467-022-35771-8,A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Taylor B, Loane M, Dolk H, Morris J, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, O'Leary M, McAllister D, Shi T, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2023,2023-01-06,Y,,,,"Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.",,doi:https://doi.org/10.1038/s41467-022-35771-8; html:https://europepmc.org/articles/PMC9821346; pdf:https://europepmc.org/articles/PMC9821346?pdf=render 34713182,https://doi.org/10.3389/fdgth.2021.711941,Cognitive Impairments in Schizophrenia: A Study in a Large Clinical Sample Using Natural Language Processing.,"Mascio A, Stewart R, Botelle R, Williams M, Mirza L, Patel R, Pollak T, Dobson R, Roberts A.",,Frontiers in digital health,2021,2021-07-15,Y,Schizophrenia; Cognition; data mining; Electronic Health Records; Natural Language Processing,,,"Background: Cognitive impairments are a neglected aspect of schizophrenia despite being a major factor of poor functional outcome. They are usually measured using various rating scales, however, these necessitate trained practitioners and are rarely routinely applied in clinical settings. Recent advances in natural language processing techniques allow us to extract such information from unstructured portions of text at a large scale and in a cost effective manner. We aimed to identify cognitive problems in the clinical records of a large sample of patients with schizophrenia, and assess their association with clinical outcomes. Methods: We developed a natural language processing based application identifying cognitive dysfunctions from the free text of medical records, and assessed its performance against a rating scale widely used in the United Kingdom, the cognitive component of the Health of the Nation Outcome Scales (HoNOS). Furthermore, we analyzed cognitive trajectories over the course of patient treatment, and evaluated their relationship with various socio-demographic factors and clinical outcomes. Results: We found a high prevalence of cognitive impairments in patients with schizophrenia, and a strong correlation with several socio-demographic factors (gender, education, ethnicity, marital status, and employment) as well as adverse clinical outcomes. Results obtained from the free text were broadly in line with those obtained using the HoNOS subscale, and shed light on additional associations, notably related to attention and social impairments for patients with higher education. Conclusions: Our findings demonstrate that cognitive problems are common in patients with schizophrenia, can be reliably extracted from clinical records using natural language processing, and are associated with adverse clinical outcomes. Harvesting the free text from medical records provides a larger coverage in contrast to neurocognitive batteries or rating scales, and access to additional socio-demographic and clinical variables. Text mining tools can therefore facilitate large scale patient screening and early symptoms detection, and ultimately help inform clinical decisions.",,doi:https://doi.org/10.3389/fdgth.2021.711941; html:https://europepmc.org/articles/PMC8521945; pdf:https://europepmc.org/articles/PMC8521945?pdf=render -36302124,https://doi.org/10.1080/21645515.2022.2127572,Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.,"Ohaeri C, Thomas DR, Salmon J, Cottrell S, Lyons J, Akbari A, Lyons RA, Torabi F, Davies GG, Williams C.",,Human vaccines & immunotherapeutics,2022,2022-10-27,Y,Vaccines; Coronavirus; Cerebral Venous Sinus Thrombosis; Cerebral Venous Thrombosis; Covid19,,,"To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.",,doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?pdf=render; doi:https://doi.org/10.1080/21645515.2022.2127572 33845766,https://doi.org/10.1186/s12879-021-05992-1,"Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality.","Flook M, Jackson C, Vasileiou E, Simpson CR, Muckian MD, Agrawal U, McCowan C, Jia Y, Murray JLK, Ritchie LD, Robertson C, Stock SJ, Wang X, Woolhouse MEJ, Sheikh A, Stagg HR.",,BMC infectious diseases,2021,2021-04-12,Y,Mortality; Review; Morbidity; Coronavirus; Systematic review; risk factors; Covid-19,,,"

Background

Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics.

Methods

Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised.

Results

One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity.

Conclusions

The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected.

Registration

This review was registered on PROSPERO as CRD42020177714 .",,doi:https://doi.org/10.1186/s12879-021-05992-1; html:https://europepmc.org/articles/PMC8040367; pdf:https://europepmc.org/articles/PMC8040367?pdf=render; pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-021-05992-1 +36302124,https://doi.org/10.1080/21645515.2022.2127572,Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.,"Ohaeri C, Thomas DR, Salmon J, Cottrell S, Lyons J, Akbari A, Lyons RA, Torabi F, Davies GG, Williams C.",,Human vaccines & immunotherapeutics,2022,2022-10-27,Y,Vaccines; Coronavirus; Cerebral Venous Sinus Thrombosis; Cerebral Venous Thrombosis; Covid19,,,"To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.",,doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?pdf=render; doi:https://doi.org/10.1080/21645515.2022.2127572 37609702,https://doi.org/10.1002/pds.5681,Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100 years using linked English primary care and hospital data.,"van Staa TP, Pirmohamed M, Sharma A, Ashcroft DM, Buchan I.",,Pharmacoepidemiology and drug safety,2023,2023-08-23,N,Adverse drug reactions; Primary Care; Medicines; Pharmacovigilance; Polypharmacy,,,"

Background

Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis-generating study was to assess the relative importance of ADR-related and emergency hospital admission for large group of medication classes.

Methods

This study was a propensity-matched case-control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65-100 with ADR-related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR-related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI).

Results

The overall population included 121 546 cases with an ADR-related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR-related code for admission diagnosis was 1.83% and 6.58% with an ADR-related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non-significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5-2.0, 18 (13.1%) between 2.0-3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR-related hospital admission (adjusted OR of 7.53 (95% CI 7.15-7.93) for those exposed to 6+ of these medicines).

Conclusions and relevance

There is a need for a regular systematic assessment of the harm-benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories.",,doi:https://doi.org/10.1002/pds.5681; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681 36448824,https://doi.org/10.1002/cpt.2807,Clinical Relevance of Drug-Drug Interactions With Antibiotics as Listed in a National Medication Formulary: Results From Two Large Population-Based Case-Control Studies in Patients Aged 65-100 Years Using Linked English Primary Care and Hospital Data.,"van Staa TP, Pirmohamed M, Sharma A, Buchan I, Ashcroft DM.",,Clinical pharmacology and therapeutics,2023,2022-12-16,Y,,,,"This study evaluated drug-drug interactions (DDIs) between antibiotic and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary based on adverse drug reaction (ADR) detectable with routine International Classification of Diseases, Tenth Revision coding. Data sources were Clinical Practice Research Databank GOLD and Aurum anonymized electronic health records from English general practices linked to hospital admission records. In propensity-matched case-control study, outcomes were ADR or emergency admissions. Analyzed were 121,546 ADR-related admission cases matched to 638,238 controls. For most antibiotics, adjusted odds ratios (aORs) for ADR-related hospital admission were large (aOR for trimethoprim 4.13; 95% confidence interval (CI), 3.97-4.30). Of the 51 DDIs evaluated for ADR-related admissions, 38 DDIs (74.5%) had statistically increased aORs of concomitant exposure compared with nonexposure (mean aOR 3.96; range 1.59-11.42); for the 89 DDIs for emergency hospital admission, the results were 75 (84.3%) and mean aOR 2.40; range 1.43-4.17. Changing reference group to single antibiotic exposure reduced aORs for concomitant exposure by 76.5% and 83.0%, respectively. Medicines listed to cause nephrotoxicity substantially increased risks that were related to number of medicines (aOR was 2.55 (95% CI, 2.46-2.64) for current use of 1 and 10.44 (95% CI, 7.36-14.81) for 3 or more medicines). In conclusion, no evidence of substantial risk was found for multiple DDIs with antibiotics despite warnings of severe outcomes in a national formulary and flagging in electronic health record software. It is proposed that the evidence base for inclusion of DDIs in national formularies be strengthened and made publicly accessible and indiscriminate flagging, which compounds alert fatigue, be reduced.",,doi:https://doi.org/10.1002/cpt.2807; html:https://europepmc.org/articles/PMC10107602; pdf:https://europepmc.org/articles/PMC10107602?pdf=render 36813664,https://doi.org/10.1016/j.injury.2023.02.029,Friction burns in cyclists: An under-recognised problem.,"Tracy LM, Gabbe BJ, Beck B.",,Injury,2023,2023-02-15,N,Cycling; Australia; Burn; New Zealand; Registry; Friction,,,"

Introduction

Cycling-related friction burns, also known as abrasions or ""road rash"", can occur when cyclists are involved in a fall or a collision. However, less is known about this type of injury as they are often overshadowed by concurrent traumatic and/or orthopaedic injuries. The aims of this project were to describe the nature and severity of friction burns in cyclists admitted to hospitals with specialist burn services in Australia and New Zealand.

Methods

A review of cycling-related friction burns recorded by the Burns Registry of Australia and New Zealand was undertaken. Summary statistics described demographic, injury event and severity, and in-hospital management data for this cohort of patients.

Results

Between July 2009 and June 2021, 143 cycling-related friction burn admissions were identified (accounting for 0.4% of all burns admissions during the study period). Seventy-six percent of patients with a cycling-related friction burn were male, and the median (interquartile range) of patients was 14 (5-41) years. The greatest proportion of cycling-related friction burns were attributed to non-collision events, namely falls (44% of all cases) and body parts being caught or coming into contact with the bicycle (27% of all cases). Although 89% of patients had a burn affecting less than five percent of their body, 71% of patients underwent a burn wound management procedure in theatre such as debridement and/or skin grafting.

Conclusions

In summary, friction burns in cyclists admitted to participating services were rare. Despite this, there remains opportunities to better understand these events to inform the development of interventions to reduce burn injury in cyclists.",,doi:https://doi.org/10.1016/j.injury.2023.02.029 34716166,https://doi.org/10.1136/bmjopen-2021-053268,Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care.,"De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths C.",,BMJ open,2021,2021-10-29,Y,Asthma; Respiratory Medicine (See Thoracic Medicine); Paediatric Thoracic Medicine,,,"

Objective

To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications.

Methods

Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework.

Participants

Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit.

Results

10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers.

Conclusions

An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma. A pilot randomised controlled trial is warranted to better estimate the effect size on adherence, with improved technical support for the EMD.",,doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"

Introduction

A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.

Methods

This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.

Results

The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.

Discussion

The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.

Conclusion

It is hoped that this framework will evolve with use and feedback.",,doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render -36769754,https://doi.org/10.3390/jcm12031106,The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.,"Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.",,Journal of clinical medicine,2023,2023-01-31,Y,irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization,,,"

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 × 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 × 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 × 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 × 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.",,doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render 31797917,https://doi.org/10.1038/s41398-019-0635-y,"Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure.","Ward J, Lyall LM, Bethlehem RAI, Ferguson A, Strawbridge RJ, Lyall DM, Cullen B, Graham N, Johnston KJA, Bailey MES, Murray GK, Smith DJ.",,Translational psychiatry,2019,2019-12-04,Y,,,,"Anhedonia is a core symptom of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of state anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson's Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson's Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including orbito-frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of state anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this phenotype as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for state anhedonia influences brain structure, including in regions associated with reward and pleasure processing.",This study assessed for genetic correlation between anhedonia and neuropsychiatric conditions. A polygenic risk score approach was applied to test for association between anhedonia and brain structure and brain function. Findings confirm that using anhedonia as a marker of vulnerability to mental illness. Findings also suggest that genetic risk for state anhedonia influences brain structure,doi:https://doi.org/10.1038/s41398-019-0635-y; html:https://europepmc.org/articles/PMC6892870; pdf:https://europepmc.org/articles/PMC6892870?pdf=render +36769754,https://doi.org/10.3390/jcm12031106,The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.,"Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.",,Journal of clinical medicine,2023,2023-01-31,Y,irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization,,,"

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 × 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 × 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 × 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 × 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.",,doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render 34514354,https://doi.org/10.1093/jamiaopen/ooab001,Transforming and evaluating electronic health record disease phenotyping algorithms using the OMOP common data model: a case study in heart failure.,"Papez V, Moinat M, Payralbe S, Asselbergs FW, Lumbers RT, Hemingway H, Dobson R, Denaxas S.",,JAMIA open,2021,2021-02-04,Y,Phenotyping; Heart Failure; Algorithms; Ehr; Omop,,,"

Objective

The aim of the study was to transform a resource of linked electronic health records (EHR) to the OMOP common data model (CDM) and evaluate the process in terms of syntactic and semantic consistency and quality when implementing disease and risk factor phenotyping algorithms.

Materials and methods

Using heart failure (HF) as an exemplar, we represented three national EHR sources (Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care, Office for National Statistics) into the OMOP CDM 5.2. We compared the original and CDM HF patient population by calculating and presenting descriptive statistics of demographics, related comorbidities, and relevant clinical biomarkers.

Results

We identified a cohort of 502 536 patients with the incident and prevalent HF and converted 1 099 195 384 rows of data from 216 581 914 encounters across three EHR sources to the OMOP CDM. The largest percentage (65%) of unmapped events was related to medication prescriptions in primary care. The average coverage of source vocabularies was >98% with the exception of laboratory tests recorded in primary care. The raw and transformed data were similar in terms of demographics and comorbidities with the largest difference observed being 3.78% in the prevalence of chronic obstructive pulmonary disease (COPD).

Conclusion

Our study demonstrated that the OMOP CDM can successfully be applied to convert EHR linked across multiple healthcare settings and represent phenotyping algorithms spanning multiple sources. Similar to previous research, challenges mapping primary care prescriptions and laboratory measurements still persist and require further work. The use of OMOP CDM in national UK EHR is a valuable research tool that can enable large-scale reproducible observational research.",,doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render 36207647,https://doi.org/10.1007/s00464-022-09682-0,"Single-centre review of the management of intra-thoracic oesophageal perforation in a tertiary oesophageal unit: paradigm shift, short- and long-term outcomes over 15 years.","Charalampakis V, Cardoso VR, Sharples A, Khalid M, Dickerson L, Wiggins T, Gkoutos GV, Tucker O, Super P, Richardson M, Nijjar R, Singhal R.",,Surgical endoscopy,2023,2022-10-07,Y,Oesophageal Perforation; Boerhaave’s; Iatrogenic Perforation,,,"

Background

Oesophageal perforation is an uncommon surgical emergency associated with high morbidity and mortality. The timing and type of intervention is crucial and there has been a major paradigm shift towards minimal invasive management over the last 15 years. Herein, we review our management of spontaneous and iatrogenic oesophageal perforations and assess the short- and long-term outcomes.

Methods

We performed a retrospective review of consecutive patients presenting with intra-thoracic oesophageal perforation between January 2004 and Dec 2020 in a single tertiary hospital.

Results

Seventy-four patients were identified with oesophageal perforations: 58.1% were male; mean age of 68.28 ± 13.67 years. Aetiology was spontaneous in 42 (56.76%), iatrogenic in 29 (39.2%) and foreign body ingestion/related to trauma in 3 (4.1%). The diagnosis was delayed in 29 (39.2%) cases for longer than 24 h. There was change in the primary diagnostic modality over the period of this study with CT being used for diagnosis for 19 of 20 patients (95%). Initial management of the oesophageal perforation included a surgical intervention in 34 [45.9%; primary closure in 28 (37.8%), resection in 6 (8.1%)], endoscopic stenting in 18 (24.3%) and conservative management in 22 (29.7%) patients. On multivariate analysis, there was an effect of pathology (malignant vs. benign; p = 0.003) and surgical treatment as first line (p = 0.048) on 90-day mortality. However, at 1-year and overall follow-up, time to presentation (≤ 24 h vs. > 24 h) remained the only significant variable (p = 0.017 & p = 0.02, respectively).

Conclusion

Oesophageal perforation remains a condition with high mortality. The paradigm shift in our tertiary unit suggests the more liberal use of CT to establish an earlier diagnosis and a higher rate of oesophageal stenting as a primary management option for iatrogenic perforations. Time to diagnosis and management continues to be the most critical variable in the overall outcome.",,doi:https://doi.org/10.1007/s00464-022-09682-0; html:https://europepmc.org/articles/PMC10017567; pdf:https://europepmc.org/articles/PMC10017567?pdf=render 37327673,https://doi.org/10.1016/j.ebiom.2023.104655,HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.,"Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.",,EBioMedicine,2023,2023-06-14,Y,Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning,,,"

Background

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.

Methods

In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.

Findings

We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).

Interpretation

Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.

Funding

EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.",,doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render @@ -689,38 +692,38 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 32855306,https://doi.org/10.1136/gutjnl-2020-321650,Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study.,"Loveday C, Sud A, Jones ME, Broggio J, Scott S, Gronthound F, Torr B, Garrett A, Nicol DL, Jhanji S, Boyce SA, Williams M, Barry C, Riboli E, Kipps E, McFerran E, Muller DC, Lyratzopoulos G, Lawler M, Abulafi M, Houlston RS, Turnbull C.",,Gut,2021,2020-08-27,Y,Colonoscopy; Colorectal Cancer; Colorectal Cancer Screening,,,"

Objective

To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic.

Design

We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval.

Results

Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%.

Conclusions

Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.",,doi:https://doi.org/10.1136/gutjnl-2020-321650; html:https://europepmc.org/articles/PMC7447105; pdf:https://europepmc.org/articles/PMC7447105?pdf=render; pdf:https://gut.bmj.com/content/gutjnl/70/6/1053.full.pdf 35139069,https://doi.org/10.1371/journal.pcbi.1009806,Known allosteric proteins have central roles in genetic disease.,"Abrusán G, Ascher DB, Inouye M.",,PLoS computational biology,2022,2022-02-09,Y,,,,"Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric sites are less conserved than active sites, and drugs targeting them are more specific than drugs binding the active sites. Here we quantify the importance of allostery in genetic disease. We show that 1) known allosteric proteins are central in disease networks, contribute to genetic disease and comorbidities much more than non-allosteric proteins, and there is an association between being allosteric and involvement in disease; 2) they are enriched in many major disease types like hematopoietic diseases, cardiovascular diseases, cancers, diabetes, or diseases of the central nervous system; 3) variants from cancer genome-wide association studies are enriched near allosteric proteins, indicating their importance to polygenic traits; and 4) the importance of allosteric proteins in disease is due, at least partly, to their central positions in protein-protein interaction networks, and less due to their dynamical properties.",,doi:https://doi.org/10.1371/journal.pcbi.1009806; html:https://europepmc.org/articles/PMC10138267; pdf:https://europepmc.org/articles/PMC10138267?pdf=render 37156754,https://doi.org/10.1111/1471-0528.17531,Risk factors for a serious adverse outcome in neonates: a retrospective cohort study of vaginal births.,"Jindal S, Steer PJ, Savvidou M, Draycott T, Dixon-Woods M, Wood A, Kim LG.",,BJOG : an international journal of obstetrics and gynaecology,2023,2023-05-08,N,risk factors; Meconium; Pyrexia; Intrapartum Fetal Monitoring; Labour Outcome; Fetal Deterioration,,,"

Objective

To investigate the hypothesis that risk factors in addition to an abnormal fetal heart rate pattern (aFHRp) are independently associated with adverse neonatal outcomes of labour.

Design

Observational prospective cohort study.

Setting

17 UK maternity units.

Sample

585 291 pregnancies between 1988 and 2000 inclusive.

Methods

Adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were estimated from multivariable logistic regression.

Main outcome measures

Adverse neonatal outcome at term (5-minute Apgar score <7, and a composite measure comprising 5-minute Apgar score <7, resuscitation by intubation and/or perinatal death).

Results

Analysis was based on 302 137 vaginal births at 37-42 weeks inclusive. We found a higher odds of Apgar score at 5 minutes <7 with suspected fetal growth restriction (OR 1.34, 95% CI 1.16-1.53), induction of labour (OR 1.41, 95% CI 1.25-1.58), nulliparity (OR 1.48, 95% CI 1.34-1.63), booking body mass index ≥30 (OR 1.18, 95% CI 1.02-1.37), maternal age <25 (OR 1.23, 95% CI 1.10-1.39), black ethnicity (OR 1.21, 95% CI 1.03-1.43), early-term birth at 37-38 weeks (OR 1.13, 95% CI 1.02-1.25), late-term birth at 41-42 weeks (OR 1.14, 95% CI 1.01-1.28), use of oxytocin (OR 1.27, 95% CI 1.14-1.41), maternal pyrexia (OR 1.87, 95% CI 1.46-2.40), aFHRp and presence of meconium (aFHRp without meconium: OR 2.40, 95% CI 2.15-2.69; meconium without aFHRp: OR 2.20, 195% CI.94-2.49; both aFHRp and meconium: OR 4.26, 95% CI 3.74-4.87). The results were similar when the composite adverse outcome was considered.

Conclusions

A range of risk factors, including suspicion of fetal growth restriction, maternal pyrexia and presence of meconium, are implicated in poor birth outcomes in addition to aFHRp. Interpretation of the fetal heart rate pattern alone is insufficient as a basis for decisions about escalation and intervention.",,doi:https://doi.org/10.1111/1471-0528.17531 +33521768,https://doi.org/10.1016/s2666-7568(20)30011-8,Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.,"Cox LS, Bellantuono I, Lord JM, Sapey E, Mannick JB, Partridge L, Gordon AL, Steves CJ, Witham MD.",,The lancet. Healthy longevity,2020,2020-11-09,Y,,,,,,doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render 36564466,https://doi.org/10.1038/s41598-022-26141-x,Assessing and removing the effect of unwanted technical variations in microbiome data.,"Fachrul M, Méric G, Inouye M, Pamp SJ, Salim A.",,Scientific reports,2022,2022-12-23,Y,,,,"Varying technologies and experimental approaches used in microbiome studies often lead to irreproducible results due to unwanted technical variations. Such variations, often unaccounted for and of unknown source, may interfere with true biological signals, resulting in misleading biological conclusions. In this work, we aim to characterize the major sources of technical variations in microbiome data and demonstrate how in-silico approaches can minimize their impact. We analyzed 184 pig faecal metagenomes encompassing 21 specific combinations of deliberately introduced factors of technical and biological variations. Using the novel Removing Unwanted Variations-III-Negative Binomial (RUV-III-NB), we identified several known experimental factors, specifically storage conditions and freeze-thaw cycles, as likely major sources of unwanted variation in metagenomes. We also observed that these unwanted technical variations do not affect taxa uniformly, with freezing samples affecting taxa of class Bacteroidia the most, for example. Additionally, we benchmarked the performances of different correction methods, including ComBat, ComBat-seq, RUVg, RUVs, and RUV-III-NB. While RUV-III-NB performed consistently robust across our sensitivity and specificity metrics, most other methods did not remove unwanted variations optimally. Our analyses suggest that a careful consideration of possible technical confounders is critical during experimental design of microbiome studies, and that the inclusion of technical replicates is necessary to efficiently remove unwanted variations computationally.",,doi:https://doi.org/10.1038/s41598-022-26141-x; html:https://europepmc.org/articles/PMC9789116; pdf:https://europepmc.org/articles/PMC9789116?pdf=render 37306981,https://doi.org/10.1001/jamaneurol.2023.1580,Independent Associations of Incident Epilepsy and Enzyme-Inducing and Non-Enzyme-Inducing Antiseizure Medications With the Development of Osteoporosis.,"Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S.",,JAMA neurology,2023,2023-08-01,N,,,,"

Importance

Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.

Objective

To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.

Design, setting, and participants

This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined.

Exposure

Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.

Main outcomes and measures

The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions.

Results

Of 8 095 441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100 000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P < .001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P < .001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P < .001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy.

Conclusions and relevance

These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.",,doi:https://doi.org/10.1001/jamaneurol.2023.1580 -33521768,https://doi.org/10.1016/s2666-7568(20)30011-8,Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.,"Cox LS, Bellantuono I, Lord JM, Sapey E, Mannick JB, Partridge L, Gordon AL, Steves CJ, Witham MD.",,The lancet. Healthy longevity,2020,2020-11-09,Y,,,,,,doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render 33619467,https://doi.org/10.1093/jamiaopen/ooaa047,A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.,"Denaxas S, Shah AD, Mateen BA, Kuan V, Quint JK, Fitzpatrick N, Torralbo A, Fatemifar G, Hemingway H.",,JAMIA open,2020,2020-12-05,Y,Phenotyping; Medical Informatics; Electronic Health Records; Uk Biobank,,,"

Objectives

The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers.

Materials and methods

We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models.

Results

We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured.

Discussion and conclusion

Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.",,doi:https://doi.org/10.1093/jamiaopen/ooaa047; html:https://europepmc.org/articles/PMC7717266; pdf:https://europepmc.org/articles/PMC7717266?pdf=render 33262478,https://doi.org/10.1038/s41433-020-01326-8,Risk factors for having diabetic retinopathy at first screening in persons with type 1 diabetes diagnosed under 18 years of age.,"Rafferty J, Owens DR, Luzio SD, Watts P, Akbari A, Thomas RL.",,"Eye (London, England)",2021,2020-12-01,N,,,,"

Objective

To determine the risk factors for having diabetic retinopathy (DR) in children and young people (CYP) with type 1 diabetes (T1DM) at first screening.

Methods

Records from the Diabetes Eye Screening Wales (DESW) service for people in Wales, UK, with T1DM diagnosed under age 18 years were combined with other electronic health record (EHR) data in the Secure Anonymised Information Linkage (SAIL) Databank. Data close to the screening date were collected, and risk factors derived from multivariate, multinomial logistic regression modelling.

Results

Data from 4172 persons, with median (lower quartile, upper quartile) age 16.3 (13.0, 22.3) years and duration of diabetes 6.6 (2.3, 12.3) years were analysed. 62.6% (n = 2613) had no DR, 26.7% (n = 1112) background DR, and 10.7% (n = 447) had referable DR (RDR). No RDR was observed under 19 years of age. Factors associated with an increased risk of DR were diabetes duration, elevated HbA1c, and diastolic blood pressure. People diagnosed with T1DM at 12 years or older had an additional risk for each year they had diabetes compared to those diagnosed before age 12 controlling for the diabetes duration (odds ratios 1.23 and 1.34, respectively).

Conclusions

This study found that 37.4% of the study cohort had DR at first screening, the risk being greater the longer the duration of diabetes or higher the HbA1c and diastolic blood pressure. In addition, people diagnosed at 12 years of age or over were more likely to have DR with each additional year with diabetes.",,doi:https://doi.org/10.1038/s41433-020-01326-8; html:https://europepmc.org/articles/PMC8452782; pdf:https://europepmc.org/articles/PMC8452782?pdf=render; doi:https://doi.org/10.1038/s41433-020-01326-8 35444210,https://doi.org/10.1038/s41698-022-00269-5,Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review.,"Kaubryte J, Lai AG.",,NPJ precision oncology,2022,2022-04-20,Y,,,,"Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (single nucleotide polymorphisms [SNPs]) associated with prognosis across 11 cancer types: lung, colorectal, breast, prostate, melanoma, renal, glioma, bladder, leukaemia, endometrial, ovarian. A systematic literature search of PubMed/MEDLINE and Europe PMC was conducted from database inception to July 1, 2021. 2497 publications from PubMed/MEDLINE and 288 preprints from Europe PMC were included. Subsequent reference and citation search was conducted and a further 39 articles added. 2824 articles were reviewed by title/abstract and 247 articles were selected for systematic review. Majority of the articles were retrospective cohort studies focusing on one cancer type, 8 articles were on pan-cancer level and 6 articles were reviews. Studies analysing clinicopathological factors included 908,567 patients and identified 238 factors, including age, gender, stage, grade, size, site, subtype, invasion, lymph nodes. Genetic studies included 210,802 patients and identified 440 gene mutations associated with cancer survival, including genes TP53, BRCA1, BRCA2, BRAF, KRAS, BIRC5. We generated a comprehensive knowledge base of biomarkers that can be used to tailor treatment according to patients' unique genetic and clinical characteristics. Our pan-cancer investigation uncovers the biomarker landscape and their combined influence that may help guide health practitioners and researchers across the continuum of cancer care from drug development to long-term survivorship.",,doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render 29716529,https://doi.org/10.1186/s12883-018-1058-8,Severe localised granulomatosis with polyangiitis (Wegener's granulomatosis) manifesting with extensive cranial nerve palsies and cranial diabetes insipidus: a case report and literature review.,"Peters JE, Gupta V, Saeed IT, Offiah C, Jawad ASM.",,BMC neurology,2018,2018-05-01,Y,Diabetes insipidus; Cyclophosphamide; pituitary; Vasculitis; Rituximab; Anca; Cavernous Sinus Syndrome; Collet-sicard Syndrome; Granulomatosis With Polyangiitis; Wegener’s Granulomatosis,,,"

Background

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem vasculitis of small- to medium-sized blood vessels. Cranial involvement can result in cranial nerve palsies and, rarely, pituitary infiltration.

Case presentation

We describe the case of a 32 year-old woman with limited but severe GPA manifesting as progressive cranial nerve palsies and pituitary dysfunction. Our patient initially presented with localised ENT involvement, but despite treatment with methotrexate, she deteriorated. Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration. The glossopharyngeal, vagus and accessory nerve palsies resulted in severe dysphagia and she required nasogastric tube feeding. Her neurological deficits substantially improved with treatment including high dose corticosteroid, cyclophosphamide and rituximab.

Conclusions

This case emphasises that serious morbidity can arise from localised cranial Wegener's granulomatosis in the absence of systemic disease. In such cases intensive induction immunosuppression is required. Analysis of previously reported cases of pituitary involvement in GPA reveals that this rare complication predominantly affects female patients.",,doi:https://doi.org/10.1186/s12883-018-1058-8; html:https://europepmc.org/articles/PMC5930853; pdf:https://europepmc.org/articles/PMC5930853?pdf=render 35940584,https://doi.org/10.1123/pes.2021-0174,Clusters of Activity-Related Social and Physical Home Environmental Factors and Their Association With Children's Home-Based Physical Activity and Sitting.,"Sheldrick MP, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,Pediatric exercise science,2023,2022-08-08,N,Families; Physical environment; Social Environment; Sedentary Behavior; Correlates; Screen Time,,,"

Purpose

Understanding which physical activity (PA) and sedentary behavior correlates cluster in children is important, particularly in the home, where children spend significant time. Therefore, this study aimed to assess clustering of physical and social activity-related factors at home, and whether these clusters are related to home-based sitting and PA in children. A secondary aim was to explore whether the clusters were associated with child, parent, and family characteristics.

Methods

Altogether, 235 children (55% girls, mean age = 10.2 [0.7] y) and their parents took part. Physical (eg, PA and electronic media equipment, house and garden size, layout) and social (eg, activity preferences, priorities, parental rules) home environmental factors were obtained via the HomeSPACE-II audit and self-report, respectively. Principal component analysis was used to identify clusters of physical and social environmental factors. Backward regression analysis and partial correlations were used to examine relationships between clusters, children's device-measured home-based activity behaviors, and background characteristics.

Results

The findings show that physical and social environment activity-related factors at home cluster. The clusters were associated with several background characteristics, with socioeconomic factors appearing to be particularly influential. The clusters were also associated with home-based activity behaviors in the hypothesized directions.

Conclusion

Interventions which target clusters of social and physical factors at home, especially among low-socioeconomic status families, are warranted.",,doi:https://doi.org/10.1123/pes.2021-0174 -36571960,https://doi.org/10.1016/j.bjps.2022.11.049,Artificial intelligence in the management and treatment of burns: A systematic review and meta-analyses.,"Taib BG, Karwath A, Wensley K, Minku L, Gkoutos GV, Moiemen N.",,"Journal of plastic, reconstructive & aesthetic surgery : JPRAS",2023,2022-11-23,N,Burns; Systematic review; Machine Learning (Ml); Artificial Intelligence (Ai); Diagnostic Test Meta Analyses,,,"

Introduction and aim

Artificial Intelligence (AI) is already being successfully employed to aid the interpretation of multiple facets of burns care. In the light of the growing influence of AI, this systematic review and diagnostic test accuracy meta-analyses aim to appraise and summarise the current direction of research in this field.

Method

A systematic literature review was conducted of relevant studies published between 1990 and 2021, yielding 35 studies. Twelve studies were suitable for a Diagnostic Test Meta-Analyses.

Results

The studies generally focussed on burn depth (Accuracy 68.9%-95.4%, Sensitivity 90.8% and Specificity 84.4%), burn segmentation (Accuracy 76.0%-99.4%, Sensitivity 97.9% and specificity 97.6%) and burn related mortality (Accuracy >90%-97.5% Sensitivity 92.9% and specificity 93.4%). Neural networks were the most common machine learning (ML) algorithm utilised in 69% of the studies. The QUADAS-2 tool identified significant heterogeneity between studies.

Discussion

The potential application of AI in the management of burns patients is promising, especially given its propitious results across a spectrum of dimensions, including burn depth, size, mortality, related sepsis and acute kidney injuries. The accuracy of the results analysed within this study is comparable to current practices in burns care.

Conclusion

The application of AI in the treatment and management of burns patients, as a series of point of care diagnostic adjuncts, is promising. Whilst AI is a potentially valuable tool, a full evaluation of its current utility and potential is limited by significant variations in research methodology and reporting.",,doi:https://doi.org/10.1016/j.bjps.2022.11.049 34161326,https://doi.org/10.1371/journal.pcbi.1009121,Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values.,"Cavallaro M, Moiz H, Keeling MJ, McCarthy ND.",,PLoS computational biology,2021,2021-06-23,Y,,,,"Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.",,doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render +36571960,https://doi.org/10.1016/j.bjps.2022.11.049,Artificial intelligence in the management and treatment of burns: A systematic review and meta-analyses.,"Taib BG, Karwath A, Wensley K, Minku L, Gkoutos GV, Moiemen N.",,"Journal of plastic, reconstructive & aesthetic surgery : JPRAS",2023,2022-11-23,N,Burns; Systematic review; Machine Learning (Ml); Artificial Intelligence (Ai); Diagnostic Test Meta Analyses,,,"

Introduction and aim

Artificial Intelligence (AI) is already being successfully employed to aid the interpretation of multiple facets of burns care. In the light of the growing influence of AI, this systematic review and diagnostic test accuracy meta-analyses aim to appraise and summarise the current direction of research in this field.

Method

A systematic literature review was conducted of relevant studies published between 1990 and 2021, yielding 35 studies. Twelve studies were suitable for a Diagnostic Test Meta-Analyses.

Results

The studies generally focussed on burn depth (Accuracy 68.9%-95.4%, Sensitivity 90.8% and Specificity 84.4%), burn segmentation (Accuracy 76.0%-99.4%, Sensitivity 97.9% and specificity 97.6%) and burn related mortality (Accuracy >90%-97.5% Sensitivity 92.9% and specificity 93.4%). Neural networks were the most common machine learning (ML) algorithm utilised in 69% of the studies. The QUADAS-2 tool identified significant heterogeneity between studies.

Discussion

The potential application of AI in the management of burns patients is promising, especially given its propitious results across a spectrum of dimensions, including burn depth, size, mortality, related sepsis and acute kidney injuries. The accuracy of the results analysed within this study is comparable to current practices in burns care.

Conclusion

The application of AI in the treatment and management of burns patients, as a series of point of care diagnostic adjuncts, is promising. Whilst AI is a potentially valuable tool, a full evaluation of its current utility and potential is limited by significant variations in research methodology and reporting.",,doi:https://doi.org/10.1016/j.bjps.2022.11.049 36446449,https://doi.org/10.1136/bmjopen-2022-061849,Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.,"Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",,BMJ open,2022,2022-11-29,Y,Primary Care; Health Policy; Covid-19,,,"

Introduction

An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.

Methods

Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.

Results

We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.

Conclusions

Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",,doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render 36976782,https://doi.org/10.1371/journal.pmed.1004204,Educational and employment outcomes associated with childhood traumatic brain injury in Scotland: A population-based record-linkage cohort study.,"Visnick MJ, Pell JP, Mackay DF, Clark D, King A, Fleming M.",,PLoS medicine,2023,2023-03-28,Y,,,,"

Background

Traumatic brain injury (TBI) is a leading cause of death and disability among young children and adolescents and the effects can be lifelong and wide-reaching. Although there have been numerous studies to evaluate the impact of childhood head injury on educational outcomes, few large-scale studies have been conducted, and previous research has been limited by issues of attrition, methodological inconsistencies, and selection bias. We aim to compare the educational and employment outcomes of Scottish schoolchildren previously hospitalised for TBI with their peers.

Methods and findings

A retrospective, record-linkage population cohort study was conducted using linkage of health and education administrative records. The cohort comprised all 766,244 singleton children born in Scotland and aged between 4 and 18 years who attended Scottish schools at some point between 2009 and 2013. Outcomes included special educational need (SEN), examination attainment, school absence and exclusion, and unemployment. The mean length of follow up from first head injury varied by outcome measure; 9.44 years for assessment of SEN and 9.53, 12.70, and 13.74 years for absenteeism and exclusion, attainment, and unemployment, respectively. Logistic regression models and generalised estimating equation (GEE) models were run unadjusted and then adjusted for sociodemographic and maternity confounders. Of the 766,244 children in the cohort, 4,788 (0.6%) had a history of hospitalisation for TBI. The mean age at first head injury admission was 3.73 years (median = 1.77 years). Following adjustment for potential confounders, previous TBI was associated with SEN (OR 1.28, CI 1.18 to 1.39, p < 0.001), absenteeism (IRR 1.09, CI 1.06 to 1.12, p < 0.001), exclusion (IRR 1.33, CI 1.15 to 1.55, p < 0.001), and low attainment (OR 1.30, CI 1.11 to 1.51, p < 0.001). The average age on leaving school was 17.14 (median = 17.37) years among children with a TBI and 17.19 (median = 17.43) among peers. Among children previously admitted for a TBI, 336 (12.2%) left school before age 16 years compared with 21,941 (10.2%) of those not admitted for TBI. There was no significant association with unemployment 6 months after leaving school (OR 1.03, CI 0.92 to 1.16, p = 0.61). Excluding hospitalisations coded as concussion strengthened the associations. We were not able to investigate age at injury for all outcomes. For TBI occurring before school age, it was impossible to be certain that SEN had not predated the TBI. Therefore, potential reverse causation was a limitation for this outcome.

Conclusions

Childhood TBI, sufficiently severe to warrant hospitalisation, was associated with a range of adverse educational outcomes. These findings reinforce the importance of preventing TBI where possible. Where not possible, children with a history of TBI should be supported to minimise the adverse impacts on their education.",,doi:https://doi.org/10.1371/journal.pmed.1004204; html:https://europepmc.org/articles/PMC10047529; pdf:https://europepmc.org/articles/PMC10047529?pdf=render 36617894,https://doi.org/10.1080/1354750x.2022.2162966,Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.,"de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",,"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",2023,2023-01-08,N,Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements,,,"IntroductionPatients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.MethodsWe conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.ResultsCases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P = 0.339). In controls, the mean cell concentration was significantly (P = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).ConclusionDespite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",,doi:https://doi.org/10.1080/1354750X.2022.2162966 36962513,https://doi.org/10.1371/journal.pgph.0000502,"Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.","Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitjà O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.",,PLOS global public health,2022,2022-09-13,Y,,,,"Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.",,doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render 34626176,https://doi.org/10.1093/brain/awab253,Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities.,"Malik R, Beaufort N, Frerich S, Gesierich B, Georgakis MK, Rannikmäe K, Ferguson AC, Haffner C, Traylor M, Ehrmann M, Sudlow CLM, Dichgans M.",,Brain : a journal of neurology,2021,2021-10-01,N,Whole-exome Sequencing; White Matter Hyperintensities; Uk Biobank; Htra1; Burden Test,,,"White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of this burden in the UK Biobank using publicly available whole-exome sequencing data (n up to 17 830) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level [c.691+2T>C, β = -0.74, standard error (SE) = 0.13, P = 9.7 × 10-9]. Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 (frequency of 1 in 275 in the UK Biobank population) to associate with an increased WMH volume (P = 5.5 × 10-6, false discovery rate = 0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; β = 0.79, SE = 0.14, P = 9.4 × 10-8). The frequency of such variants in the UK Biobank population was 1 in 450. The WMH volume was brought forward by ∼11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (β = 0.26, SE = 0.02, P = 2.9 × 10-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (β = 0.44, SE = 0.14, P = 0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (P = 1.5 × 10-4, false discovery rate = 0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (odds ratio = 12.24, 95%CI: 2.54-35.25; P = 8.3 × 10-5]. Collectively, these findings highlight an important role of rare genetic variation and the HTRA1 protease in determining WMH burden in the general population.",,doi:https://doi.org/10.1093/brain/awab253; html:https://europepmc.org/articles/PMC8557338; pdf:https://europepmc.org/articles/PMC8557338?pdf=render; doi:https://doi.org/10.1093/brain/awab253 33320878,https://doi.org/10.1371/journal.pone.0243843,Developing a national birth cohort for child health research using a hospital admissions database in England: The impact of changes to data collection practices.,"Zylbersztejn A, Gilbert R, Hardelid P.",,PloS one,2020,2020-12-15,Y,,,,"

Background

National birth cohorts derived from administrative health databases constitute unique resources for child health research due to whole country coverage, ongoing follow-up and linkage to other data sources. In England, a national birth cohort can be developed using Hospital Episode Statistics (HES), an administrative database covering details of all publicly funded hospital activity, including 97% of births, with longitudinal follow-up via linkage to hospital and mortality records. We present methods for developing a national birth cohort using HES and assess the impact of changes to data collection over time on coverage and completeness of linked follow-up records for children.

Methods

We developed a national cohort of singleton live births in 1998-2015, with information on key risk factors at birth (birth weight, gestational age, maternal age, ethnicity, area-level deprivation). We identified three changes to data collection, which could affect linkage of births to follow-up records: (1) the introduction of the ""NHS Numbers for Babies (NN4B)"", an on-line system which enabled maternity staff to request a unique healthcare patient identifier (NHS number) immediately at birth rather than at civil registration, in Q4 2002; (2) the introduction of additional data quality checks at civil registration in Q3 2009; and (3) correcting a postcode extraction error for births by the data provider in Q2 2013. We evaluated the impact of these changes on trends in two outcomes in infancy: hospital readmissions after birth (using interrupted time series analyses) and mortality rates (compared to published national statistics).

Results

The cohort covered 10,653,998 babies, accounting for 96% of singleton live births in England in 1998-2015. Overall, 2,077,929 infants (19.5%) had at least one hospital readmission after birth. Readmission rates declined by 0.2% percentage points per annual quarter in Q1 1998 to Q3 2002, shifted up by 6.1% percentage points (compared to the expected value based on the trend before Q4 2002) to 17.7% in Q4 2002 when NN4B was introduced, and increased by 0.1% percentage points per annual quarter thereafter. Infant mortality rates were under-reported by 16% for births in 1998-2002 and similar to published national mortality statistics for births in 2003-2015. The trends in infant readmission were not affected by changes to data collection practices in Q3 2009 and Q2 2013, but the proportion of unlinked mortality records in HES and in ONS further declined after 2009.

Discussion

HES can be used to develop a national birth cohort for child health research with follow-up via linkage to hospital and mortality records for children born from 2003 onwards. Re-linking births before 2003 to their follow-up records would maximise potential benefits of this rich resource, enabling studies of outcomes in adolescents with over 20 years of follow-up.",,doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render +29938349,https://doi.org/10.1007/s11892-018-1021-5,Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment.,"Strawbridge RJ, van Zuydam NR.",,Current diabetes reports,2018,2018-06-25,Y,Type 2 diabetes; Ischemic stroke; coronary artery disease; risk factors; Peripheral Artery Disease; Genetics; Mendelian Randomisation,,,"

Purpose of review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.",,doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render 35896970,https://doi.org/10.1186/s12879-022-07628-4,SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2.,"Eales O, Page AJ, de Oliveira Martins L, Wang H, Bodinier B, Haw D, Jonnerby J, Atchison C, COVID-19 Genomics UK (COG-UK) Consortium, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Chadeau-Hyam M, Donnelly CA, Elliott P.",,BMC infectious diseases,2022,2022-07-27,Y,Mutation; Genetic diversity; Transmission Advantage; Covid-19; Sars-cov-2; Delta Variant,,,"

Background

Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape.

Methods

We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September-27 September 2021) and 15 (19 October-5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.

Results

We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.

Conclusions

As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.",,doi:https://doi.org/10.1186/s12879-022-07628-4; html:https://europepmc.org/articles/PMC9326417; pdf:https://europepmc.org/articles/PMC9326417?pdf=render 35012379,https://doi.org/10.1177/17407745211069985,Protecting blinded trials in electronic hospital systems.,"Sydes MR, Wong WK, Bakhai A, Joffe N, Love SB.",,"Clinical trials (London, England)",2022,2022-01-11,Y,,,,,,doi:https://doi.org/10.1177/17407745211069985; html:https://europepmc.org/articles/PMC9036147; pdf:https://europepmc.org/articles/PMC9036147?pdf=render -29938349,https://doi.org/10.1007/s11892-018-1021-5,Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment.,"Strawbridge RJ, van Zuydam NR.",,Current diabetes reports,2018,2018-06-25,Y,Type 2 diabetes; Ischemic stroke; coronary artery disease; risk factors; Peripheral Artery Disease; Genetics; Mendelian Randomisation,,,"

Purpose of review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.",,doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render 32310142,https://doi.org/10.2196/14306,"Objective Characterization of Activity, Sleep, and Circadian Rhythm Patterns Using a Wrist-Worn Actigraphy Sensor: Insights Into Posttraumatic Stress Disorder.","Tsanas A, Woodward E, Ehlers A.",,JMIR mHealth and uHealth,2020,2020-04-20,Y,Sleep; Posttraumatic Stress Disorder; actigraphy; Wearable Technology; Geneactiv,,,"

Background

Wearables have been gaining increasing momentum and have enormous potential to provide insights into daily life behaviors and longitudinal health monitoring. However, to date, there is still a lack of principled algorithmic framework to facilitate the analysis of actigraphy and objectively characterize day-by-day data patterns, particularly in cohorts with sleep problems.

Objective

This study aimed to propose a principled algorithmic framework for the assessment of activity, sleep, and circadian rhythm patterns in people with posttraumatic stress disorder (PTSD), a mental disorder with long-lasting distressing symptoms such as intrusive memories, avoidance behaviors, and sleep disturbance. In clinical practice, these symptoms are typically assessed using retrospective self-reports that are prone to recall bias. The aim of this study was to develop objective measures from patients' everyday lives, which could potentially considerably enhance the understanding of symptoms, behaviors, and treatment effects.

Methods

Using a wrist-worn sensor, we recorded actigraphy, light, and temperature data over 7 consecutive days from three groups: 42 people diagnosed with PTSD, 43 traumatized controls, and 30 nontraumatized controls. The participants also completed a daily sleep diary over 7 days and the standardized Pittsburgh Sleep Quality Index questionnaire. We developed a novel approach to automatically determine sleep onset and offset, which can also capture awakenings that are crucial for assessing sleep quality. Moreover, we introduced a new intuitive methodology facilitating actigraphy exploration and characterize day-by-day data across 49 activity, sleep, and circadian rhythm patterns.

Results

We demonstrate that the new sleep detection algorithm closely matches the sleep onset and offset against the participants' sleep diaries consistently outperforming an existing open-access widely used approach. Participants with PTSD exhibited considerably more fragmented sleep patterns (as indicated by greater nocturnal activity, including awakenings) and greater intraday variability compared with traumatized and nontraumatized control groups, showing statistically significant (P<.05) and strong associations (|R|>0.3).

Conclusions

This study lays the foundation for objective assessment of activity, sleep, and circadian rhythm patterns using passively collected data from a wrist-worn sensor, facilitating large community studies to monitor longitudinally healthy and pathological cohorts under free-living conditions. These findings may be useful in clinical PTSD assessment and could inform therapy and monitoring of treatment effects.",,doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134 35964473,https://doi.org/10.1016/j.socscimed.2022.115237,"""We've all got the virus inside us now"": Disaggregating public health relations and responsibilities for health protection in pandemic London.","Kasstan B, Mounier-Jack S, Gaskell KM, Eggo RM, Marks M, Chantler T.",,Social science & medicine (1982),2022,2022-08-07,Y,Pandemic; Public Health; Judaism; Responsibility; London; Covid-19,,,"The COVID-19 pandemic has disproportionately impacted ethnic minorities in the global north, evidenced by higher rates of transmission, morbidity, and mortality relative to population sizes. Orthodox Jewish neighbourhoods in London had extremely high SARS-CoV-2 seroprevalence rates, reflecting patterns in Israel and the US. The aim of this paper is to examine how responsibilities over health protection are conveyed, and to what extent responsibility is sought by, and shared between, state services, and 'community' stakeholders or representative groups, and families in public health emergencies. The study investigates how public health and statutory services stakeholders, Orthodox Jewish communal custodians and households sought to enact health protection in London during the first year of the pandemic (March 2020-March 2021). Twenty-eight semi-structured interviews were conducted across these cohorts. Findings demonstrate that institutional relations - both their formation and at times fragmentation - were directly shaped by issues surrounding COVID-19 control measures. Exchanges around protective interventions (whether control measures, contact tracing technologies, or vaccines) reveal diverse and diverging attributions of responsibility and authority. The paper develops a framework of public health relations to understand negotiations between statutory services and minority groups over responsiveness and accountability in health protection. Disaggregating public health relations can help social scientists to critique who and what characterises institutional relationships with minority groups, and what ideas of responsibility and responsiveness are projected by differently-positioned stakeholders in health protection.",,doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render 36812613,https://doi.org/10.1371/journal.pdig.0000190,Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.,"Groenhof TKJ, Haitjema S, Lely AT, Grobbee DE, Asselbergs FW, Bots ML, UCC-CVRM and UPOD Study groups.",,PLOS digital health,2023,2023-02-08,Y,,,,"Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).",,doi:https://doi.org/10.1371/journal.pdig.0000190; html:https://europepmc.org/articles/PMC9931327; pdf:https://europepmc.org/articles/PMC9931327?pdf=render 37191413,https://doi.org/10.14336/ad.2022.1107,Conceptual Overview of Biological Age Estimation.,"Salih A, Nichols T, Szabo L, Petersen SE, Raisi-Estabragh Z.",,Aging and disease,2023,2023-06-01,Y,,,,"Chronological age is an imperfect measure of the aging process, which is affected by a wide range of genetic and environmental exposures. Biological age estimates may be derived using mathematical modelling with biomarkers set as predictors and chronological age as the output. The difference between biological and chronological age is denoted the ""age gap"" and considered a complementary indicator of aging. The utility of the ""age gap"" metric is assessed through examination of its associations with exposures of interest and the demonstration of additional information provided by this metric over chronological age alone. This paper reviews the key concepts of biological age estimation, the age gap metric, and approaches to assessment of model performance in this context. We further discuss specific challenges for the field, in particular the limited generalisability of effect sizes across studies owing to dependency of the age gap metric on pre-processing and model building methods. The discussion will be centred on brain age estimation, but the concepts are transferable to all biological age estimation.",,doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?pdf=render 36529816,https://doi.org/10.1038/s41598-022-26357-x,Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.,"Mulick AR, Henderson AD, Prieto-Merino D, Mansfield KE, Matthewman J, Quint JK, Lyons RA, Sheikh A, McAllister DA, Nitsch D, Langan SM.",,Scientific reports,2022,2022-12-18,Y,,,,"Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.",,doi:https://doi.org/10.1038/s41598-022-26357-x; html:https://europepmc.org/articles/PMC9760185; pdf:https://europepmc.org/articles/PMC9760185?pdf=render 34044910,https://doi.org/10.1016/bs.acc.2020.08.002,Translational biomarkers in the era of precision medicine.,"Bravo-Merodio L, Acharjee A, Russ D, Bisht V, Williams JA, Tsaprouni LG, Gkoutos GV.",,Advances in clinical chemistry,2021,2020-10-03,N,Artificial intelligence; Clinical Trials; Omics; Big Data; Translational Biomarkers,,,"In this chapter we discuss the past, present and future of clinical biomarker development. We explore the advent of new technologies, paving the way in which health, medicine and disease is understood. This review includes the identification of physicochemical assays, current regulations, the development and reproducibility of clinical trials, as well as, the revolution of omics technologies and state-of-the-art integration and analysis approaches.",,doi:https://doi.org/10.1016/bs.acc.2020.08.002 -33413610,https://doi.org/10.1186/s13073-020-00822-6,An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.,"Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.",,Genome medicine,2021,2021-01-07,Y,Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus,,,"During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online ""immuno-analytics"" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).",,doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render 34158612,https://doi.org/10.1038/s41366-021-00846-x,Effects of increased body mass index on employment status: a Mendelian randomisation study.,"Campbell DD, Green M, Davies N, Demou E, Ward J, Howe LD, Harrison S, Johnston KJA, Strawbridge RJ, Popham F, Smith DJ, Munafò MR, Katikireddi SV.",,International journal of obesity (2005),2021,2021-06-22,Y,,,,"

Background

The obesity epidemic may have substantial implications for the global workforce, including causal effects on employment, but clear evidence is lacking. Obesity may prevent people from being in paid work through poor health or through social discrimination. We studied genetic variants robustly associated with body mass index (BMI) to investigate its causal effects on employment.

Dataset/methods

White UK ethnicity participants of working age (men 40-64 years, women 40-59 years), with suitable genetic data were selected in the UK Biobank study (N = 230,791). Employment status was categorised in two ways: first, contrasting being in paid employment with any other status; and second, contrasting being in paid employment with sickness/disability, unemployment, early retirement and caring for home/family. Socioeconomic indicators also investigated were hours worked, household income, educational attainment and Townsend deprivation index (TDI). We conducted observational and two-sample Mendelian randomisation (MR) analyses to investigate the effect of increased BMI on employment-related outcomes.

Results

Regressions showed BMI associated with all the employment-related outcomes investigated. MR analyses provided evidence for higher BMI causing increased risk of sickness/disability (OR 1.08, 95% CI 1.04, 1.11, per 1 Kg/m2 BMI increase) and decreased caring for home/family (OR 0.96, 95% CI 0.93, 0.99), higher TDI (Beta 0.038, 95% CI 0.018, 0.059), and lower household income (OR 0.98, 95% CI 0.96, 0.99). In contrast, MR provided evidence for no causal effect of BMI on unemployment, early retirement, non-employment, hours worked or educational attainment. There was little evidence for causal effects differing by sex or age. Robustness tests yielded consistent results.

Discussion

BMI appears to exert a causal effect on employment status, largely by affecting an individual's health rather than through increased unemployment arising from social discrimination. The obesity epidemic may be contributing to increased worklessness and therefore could impose a substantial societal burden.",,doi:https://doi.org/10.1038/s41366-021-00846-x; html:https://europepmc.org/articles/PMC8310793; pdf:https://europepmc.org/articles/PMC8310793?pdf=render +33413610,https://doi.org/10.1186/s13073-020-00822-6,An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.,"Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.",,Genome medicine,2021,2021-01-07,Y,Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus,,,"During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online ""immuno-analytics"" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).",,doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render 34266851,https://doi.org/10.1136/bmjhci-2021-100356,Development of a core competency framework for clinical informatics. ,"Davies A, Mueller J, Hassey A, Moulton G.",,BMJ health & care informatics,2021,2021-07-01,Y,,,,"Until this point there was no national core competency framework for clinical informatics in the UK. We report on the final two iterations of work carried out in the formation of a national core competency framework. This follows an initial systematic literature review of existing skills and competencies and a job listing analysis.MethodsAn iterative approach was applied to framework development. Using a mixed-methods design we carried out semi-structured interviews with participants involved in informatics (n=15). The framework was updated based on the interview findings and was subsequently distributed as part of a bespoke online digital survey for wider participation (n=87). The final version of the framework is based on the findings of the survey. Over 102 people reviewed the framework as part of the interview or survey process. This led to a final core competency framework containing 6 primary domains with 36 subdomains containing 111 individual competencies. An iterative mixed-methods approach for competency development involving the target community was appropriate for development of the competency framework. There is some contention around the depth of technical competencies required. Care is also needed to avoid professional burnout, as clinicians and healthcare practitioners already have clinical competencies to maintain. Therefore, how the framework is applied in practice and how practitioners meet the competencies requires careful consideration.",,doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render +30423068,https://doi.org/10.1093/bioinformatics/bty605,Ontology-based validation and identification of regulatory phenotypes.,"Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,"Bioinformatics (Oxford, England)",2018,2018-09-01,Y,,"Applied Analytics, The Human Phenome",,"

Motivation

Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.

Results

We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.

Availability and implementation

https://github.com/bio-ontology-research-group/phenogocon.",,doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render; pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf +33710281,https://doi.org/10.1093/ageing/afab060,COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).,"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hayward A, Shallcross L.",,Age and ageing,2021,2021-06-01,Y,Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render 35277405,https://doi.org/10.1136/bmjopen-2021-055070,Predictors of falls and fractures leading to hospitalisation in 36 101 people with affective disorders: a large representative cohort study.,"Ma R, Perera G, Romano E, Vancampfort D, Koyanagi A, Stewart R, Mueller C, Stubbs B.",,BMJ open,2022,2022-03-11,Y,Mental health; Anxiety Disorders; Adult Psychiatry; Depression & Mood Disorders,,,"

Objectives

To investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders.

Design

Cohort study.

Setting

The South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register.

Participants

A large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30-F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register.

Primary and secondary outcome measures

Falls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures.

Results

Of 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures.

Conclusions

Over a mean 5 years' follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group.",,doi:https://doi.org/10.1136/bmjopen-2021-055070; html:https://europepmc.org/articles/PMC8919445; pdf:https://europepmc.org/articles/PMC8919445?pdf=render 33112263,https://doi.org/10.1530/eje-20-0296,Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review.,"Subramanian A, Idkowiak J, Toulis KA, Thangaratinam S, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-01-01,Y,,,,"

Context

The incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.

Objective

To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.

Data sources

We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.

Study selection and extraction

Two reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.

Results

Seven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.

Conclusions

Pubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.",,doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render -33710281,https://doi.org/10.1093/ageing/afab060,COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).,"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hayward A, Shallcross L.",,Age and ageing,2021,2021-06-01,Y,Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render -30423068,https://doi.org/10.1093/bioinformatics/bty605,Ontology-based validation and identification of regulatory phenotypes.,"Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,"Bioinformatics (Oxford, England)",2018,2018-09-01,Y,,"Applied Analytics, The Human Phenome",,"

Motivation

Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.

Results

We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.

Availability and implementation

https://github.com/bio-ontology-research-group/phenogocon.",,doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render; pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf 31616478,https://doi.org/10.3389/fgene.2019.00922,Machine Learning Predicts Accurately Mycobacterium tuberculosis Drug Resistance From Whole Genome Sequencing Data.,"Deelder W, Christakoudi S, Phelan J, Benavente ED, Campino S, McNerney R, Palla L, Clark TG.",,Frontiers in genetics,2019,2019-09-26,Y,Mycobacterium tuberculosis; Drug resistance; Mdr-tb; Xdr-tb; Machine Learning,Applied Analytics,,"Background: Tuberculosis disease, caused by Mycobacterium tuberculosis, is a major public health problem. The emergence of M. tuberculosis strains resistant to existing treatments threatens to derail control efforts. Resistance is mainly conferred by mutations in genes coding for drug targets or converting enzymes, but our knowledge of these mutations is incomplete. Whole genome sequencing (WGS) is an increasingly common approach to rapidly characterize isolates and identify mutations predicting antimicrobial resistance and thereby providing a diagnostic tool to assist clinical decision making. Methods: We applied machine learning approaches to 16,688 M. tuberculosis isolates that have undergone WGS and laboratory drug-susceptibility testing (DST) across 14 antituberculosis drugs, with 22.5% of samples being multidrug resistant and 2.1% being extensively drug resistant. We used non-parametric classification-tree and gradient-boosted-tree models to predict drug resistance and uncover any associated novel putative mutations. We fitted separate models for each drug, with and without ""co-occurrent resistance"" markers known to be causing resistance to drugs other than the one of interest. Predictive performance was measured using sensitivity, specificity, and the area under the receiver operating characteristic curve, assuming DST results as the gold standard. Results: The predictive performance was highest for resistance to first-line drugs, amikacin, kanamycin, ciprofloxacin, moxifloxacin, and multidrug-resistant tuberculosis (area under the receiver operating characteristic curve above 96%), and lowest for third-line drugs such as D-cycloserine and Para-aminosalisylic acid (area under the curve below 85%). The inclusion of co-occurrent resistance markers led to improved performance for some drugs and superior results when compared to similar models in other large-scale studies, which had smaller sample sizes. Overall, the gradient-boosted-tree models performed better than the classification-tree models. The mutation-rank analysis detected no new single nucleotide polymorphisms linked to drug resistance. Discordance between DST and genotypically inferred resistance may be explained by DST errors, novel rare mutations, hetero-resistance, and nongenomic drivers such as efflux-pump upregulation. Conclusion: Our work demonstrates the utility of machine learning as a flexible approach to drug resistance prediction that is able to accommodate a much larger number of predictors and to summarize their predictive ability, thus assisting clinical decision making and single nucleotide polymorphism detection in an era of increasing WGS data generation.",,doi:https://doi.org/10.3389/fgene.2019.00922; html:https://europepmc.org/articles/PMC6775242; pdf:https://europepmc.org/articles/PMC6775242?pdf=render 33402395,https://doi.org/10.1136/jech-2020-215204,Hospital readmission among people experiencing homelessness in England: a cohort study of 2772 matched homeless and housed inpatients.,"Lewer D, Menezes D, Cornes M, Blackburn RM, Byng R, Clark M, Denaxas S, Evans H, Fuller J, Hewett N, Kilmister A, Luchenski SA, Manthorpe J, McKee M, Neale J, Story A, Tinelli M, Whiteford M, Wurie F, Yavlinsky A, Hayward A, Aldridge R.",,Journal of epidemiology and community health,2021,2021-01-05,Y,Homelessness; Health Inequalities; Record Linkage; Access To Hlth Care,,,"

Background

Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission.

Methods

We conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios.

Results

After adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients.

Conclusions

Hospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs.",,doi:https://doi.org/10.1136/jech-2020-215204; html:https://europepmc.org/articles/PMC8223662; pdf:https://europepmc.org/articles/PMC8223662?pdf=render; pdf:https://jech.bmj.com/content/jech/75/7/681.full.pdf 36082449,https://doi.org/10.1002/ijc.34279,"Global colorectal cancer research, 2007-2021: Outputs and funding. ","Begum M, Lewison G, Wang X, Dunne PD, Maughan T, Sullivan R, Lawler M.",,International journal of cancer,2023,2022-09-28,Y,,,,"The purpose of this study was to provide an evidence base for colorectal cancer research activity that might influence policy, mainly at the national level. Improvements in healthcare delivery have lengthened life expectancy, but within a situation of increased cancer incidence. The disease burden of CRC has risen significantly, particularly in Africa, Asia and Latin America. Research is key to its control and reduction, but few studies have delineated the volume and funding of global research on CRC. We identified research papers in the Web of Science (WoS) from 2007 to 2021, and determined the contributions of the leading countries, the research domains studied, and their sources of funding. We identified 62 716 papers, representing 5.7% of all cancer papers. This percentage was somewhat disproportionate to the disease burden (7.7% in 2015), especially in Eastern Europe. International collaboration increased over the time period in almost all countries except in China. Genetics, surgery and prognosis were the leading research domains. However, research on palliative care and quality-of-life in CRC was lacking. In Western Europe, the main funding source was the charity sector, particularly in the UK, but in most other countries government played the leading role, especially in China and the USA. There was little support from industry. Several Asian countries provided minimal contestable funding, which may have reduced the impact of their CRC research. Certain countries must perform more CRC research overall, especially in domains such as screening, palliative care and quality-of-life. The private-non-profit sector should be an alternative source of support.",,doi:https://doi.org/10.1002/ijc.34279; html:https://europepmc.org/articles/PMC10086800; pdf:https://europepmc.org/articles/PMC10086800?pdf=render @@ -742,8 +745,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 36712153,https://doi.org/10.1093/ehjdh/ztac046,Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.,"Wang X, Mobley AR, Tica O, Okoth K, Ghosh RE, Myles P, Williams T, Haynes S, Nirantharakumar K, Shukla D, Kotecha D, DaRe2THINK Trial Committees .",,European heart journal. Digital health,2022,2022-09-16,Y,Coding; Anticoagulation; Atrial fibrillation; Randomized controlled trial; Primary Care; Secondary Care; Electronic Healthcare Record,,,"

Aims

Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research.

Methods and results

The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality).

Conclusion

Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.",,doi:https://doi.org/10.1093/ehjdh/ztac046; html:https://europepmc.org/articles/PMC9708037; pdf:https://europepmc.org/articles/PMC9708037?pdf=render; pdf:https://academic.oup.com/ehjdh/article-pdf/3/3/426/47117043/ztac046.pdf 35085490,https://doi.org/10.1016/s2213-2600(21)00542-7,SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys.,"Chadeau-Hyam M, Wang H, Eales O, Haw D, Bodinier B, Whitaker M, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Donnelly CA, Elliott P, COVID-19 Genomics UK consortium.",,The Lancet. Respiratory medicine,2022,2022-01-24,Y,,,,"

Background

England has experienced a third wave of the COVID-19 epidemic since the end of May, 2021, coinciding with the rapid spread of the delta (B.1.617.2) variant, despite high levels of vaccination among adults. Vaccination rates (single dose) in England are lower among children aged 16-17 years and 12-15 years, whose vaccination in England commenced in August and September, 2021, respectively. We aimed to analyse the underlying dynamics driving patterns in SARS-CoV-2 prevalence during September, 2021, in England.

Methods

The REal-time Assessment of Community Transmission-1 (REACT-1) study, which commenced data collection in May, 2020, involves a series of random cross-sectional surveys in the general population of England aged 5 years and older. Using RT-PCR swab positivity data from 100 527 participants with valid throat and nose swabs in round 14 of REACT-1 (Sept 9-27, 2021), we estimated community-based prevalence of SARS-CoV-2 and vaccine effectiveness against infection by combining round 14 data with data from round 13 (June 24 to July 12, 2021; n=172 862).

Findings

During September, 2021, we estimated a mean RT-PCR positivity rate of 0·83% (95% CrI 0·76-0·89), with a reproduction number (R) overall of 1·03 (95% CrI 0·94-1·14). Among the 475 (62·2%) of 764 sequenced positive swabs, all were of the delta variant; 22 (4·63%; 95% CI 3·07-6·91) included the Tyr145His mutation in the spike protein associated with the AY.4 sublineage, and there was one Glu484Lys mutation. Age, region, key worker status, and household size jointly contributed to the risk of swab positivity. The highest weighted prevalence was observed among children aged 5-12 years, at 2·32% (95% CrI 1·96-2·73) and those aged 13-17 years, at 2·55% (2·11-3·08). The SARS-CoV-2 epidemic grew in those aged 5-11 years, with an R of 1·42 (95% CrI 1·18-1·68), but declined in those aged 18-54 years, with an R of 0·81 (0·68-0·97). At ages 18-64 years, the adjusted vaccine effectiveness against infection was 62·8% (95% CI 49·3-72·7) after two doses compared to unvaccinated people, for all vaccines combined, 44·8% (22·5-60·7) for the ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine, and 71·3% (56·6-81·0) for the BNT162b2 (Pfizer-BioNTech) vaccine. In individuals aged 18 years and older, the weighted prevalence of swab positivity was 0·35% (95% CrI 0·31-0·40) if the second dose was administered up to 3 months before their swab but 0·55% (0·50-0·61) for those who received their second dose 3-6 months before their swab, compared to 1·76% (1·60-1·95) among unvaccinated individuals.

Interpretation

In September, 2021, at the start of the autumn school term in England, infections were increasing exponentially in children aged 5-17 years, at a time when vaccination rates were low in this age group. In adults, compared to those who received their second dose less than 3 months ago, the higher prevalence of swab positivity at 3-6 months following two doses of the COVID-19 vaccine suggests an increased risk of breakthrough infections during this period. The vaccination programme needs to reach children as well as unvaccinated and partially vaccinated adults to reduce SARS-CoV-2 transmission and associated disruptions to work and education.

Funding

Department of Health and Social Care, England.",,doi:https://doi.org/10.1016/S2213-2600(21)00542-7; html:https://europepmc.org/articles/PMC8786320 36834176,https://doi.org/10.3390/ijerph20043477,"Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.","Chandan JS, Brown KR, Simms-Williams N, Bashir NZ, Camaradou J, Heining D, Turner GM, Rivera SC, Hotham R, Minhas S, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Marshall T, Calvert MJ, Haroon S, Aiyegbusi OL, TLC Study.",,International journal of environmental research and public health,2023,2023-02-16,Y,Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-Viral Syndromes; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc),,,"

Background

Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.

Methods

We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.

Findings

Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.

Interpretation

In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.

Registration

The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render -35296643,https://doi.org/10.1038/s41467-022-28517-z,"Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.","Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.",,Nature communications,2022,2022-03-16,Y,,,,"Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.",,doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render; pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf 35898465,https://doi.org/10.3389/fendo.2022.888924,Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.,"Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.",,Frontiers in endocrinology,2022,2022-07-11,Y,Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination,,,"

Aim

We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.

Methods

This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.

Results

Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).

Conclusion

Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.",,doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render +35296643,https://doi.org/10.1038/s41467-022-28517-z,"Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.","Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.",,Nature communications,2022,2022-03-16,Y,,,,"Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.",,doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render; pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf 35765786,https://doi.org/10.7189/jogh.12.04052,"Global, regional, and national prevalence of asthma in 2019: a systematic analysis and modelling study.","Song P, Adeloye D, Salim H, Dos Santos JP, Campbell H, Sheikh A, Rudan I.",,Journal of global health,2022,2022-06-29,Y,,,,"

Background

Asthma has a significant impact on people of all ages, particularly children. A lack of universally accepted case definition and confirmatory tests and a poor understanding of major risks interfere with a global response. We aimed to provide global estimates of asthma prevalence and cases in 2019 across four main epidemiological case definitions - current wheezing, ever wheezing, current asthma, and ever asthma. We further investigated major associated factors to determine regional and national distributions of prevalence and cases for current wheezing and ever asthma.

Methods

We identified relevant population-based studies published between January 1, 1990, and December 31, 2019. Using a multilevel multivariable mixed-effects meta-regression model, we assessed the age- and sex-adjusted associations of asthma with study-level variables, including year, setting, region and socio-demographic index (SDI). Using a random-effects meta-analysis, we then identified risk factors for current wheezing and asthma. From a ""risk factor-based model"", which included current smoking, and biomass exposure for current wheezing, and rural setting, current smoking, biomass exposure, and SDI for ever asthma, we estimated case numbers and prevalence across regions and 201 countries and territories in 2019.

Results

220 population-based studies conducted in 88 countries were retained. In 2019, the global prevalence estimates of asthma in people aged 5-69 years by various definitions, namely current wheezing, ever wheezing, current asthma, and ever asthma were 11.5% (95% confidence interval (CI) = 9.1-14.3), 17.9% (95% CI = 14.2-22.3), 5.4% (95% CI = 3.2-9.0) and 9.8% (95% CI = 7.8-12.2), respectively. These translated to 754.6 million (95% CI = 599. 7-943.4), 1181.3 million (95% CI = 938.0-1,471.0), 357.4 million (95% CI = 213.0-590.8), 645.2 million (95% CI = 513.1-806.2) cases, respectively. The overall prevalence of current wheezing among people aged 5-69 years was the highest in the African Region at 13.2% (95% CI = 10.5-16.5), and the lowest in the Americas Region at 10.0% (95% CI = 8.0-12.5). For ever asthma, the estimated prevalence in those aged 5-69 years was also the highest in the African Region at 11.3% (95% CI = 9.0-14.1), but the lowest in South-East Asia Region (8.8, 95% CI = 7.0-11.0).

Conclusions

Although varying approaches to case identification in different settings make epidemiological estimates of asthma very difficult, this analysis reaffirms asthma as a common global respiratory condition before the COVID-19 pandemic in 2019, with higher prevalence than previously reported in many world settings.",,doi:https://doi.org/10.7189/jogh.12.04052; html:https://europepmc.org/articles/PMC9239324; pdf:https://europepmc.org/articles/PMC9239324?pdf=render 33722197,https://doi.org/10.1186/s12879-021-05951-w,Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.,"Haroon S, Subramanian A, Cooper J, Anand A, Gokhale K, Byne N, Dhalla S, Acosta-Mena D, Taverner T, Okoth K, Wang J, Chandan JS, Sainsbury C, Zemedikun DT, Thomas GN, Parekh D, Marshall T, Sapey E, Adderley NJ, Nirantharakumar K.",,BMC infectious diseases,2021,2021-03-15,Y,,,,"

Introduction

Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality.

Methods

We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome.

Results

The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality.

Conclusion

Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.",,doi:https://doi.org/10.1186/s12879-021-05951-w; html:https://europepmc.org/articles/PMC7957446; pdf:https://europepmc.org/articles/PMC7957446?pdf=render 35297226,https://doi.org/10.1002/jcsm.12971,Association of shorter leucocyte telomere length with risk of frailty.,"Bountziouka V, Nelson CP, Codd V, Wang Q, Musicha C, Allara E, Kaptoge S, Di Angelantonio E, Butterworth AS, Thompson JR, Curtis EM, Wood AM, Danesh JN, Harvey NC, Cooper C, Samani NJ.",,"Journal of cachexia, sarcopenia and muscle",2022,2022-03-17,Y,Frailty; Biological Age; Uk Biobank; Leucocyte Telomere Length,,,"

Background

Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty.

Methods

We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal.

Results

Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10-33 ), more likely to be female (61%, P = 1.97 × 10-129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10-111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10-12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10-30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13).

Conclusions

Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.",,doi:https://doi.org/10.1002/jcsm.12971; html:https://europepmc.org/articles/PMC9178164; pdf:https://europepmc.org/articles/PMC9178164?pdf=render @@ -762,8 +765,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 35997594,https://doi.org/10.1099/mic.0.001223,Diagnostic MALDI-TOF MS can differentiate between high and low toxic Staphylococcus aureus bacteraemia isolates as a predictor of patient outcome.,"Brignoli T, Recker M, Lee WWY, Dong T, Bhamber R, Albur M, Williams P, Dowsey AW, Massey RC.",,"Microbiology (Reading, England)",2022,2022-08-01,Y,Toxicity; Staphylococcus aureus; Bacteraemia; agr; Maldi-tof Ms Diagnosis,,,"Staphylococcus aureus bacteraemia (SAB) is a major cause of blood-stream infection (BSI) in both healthcare and community settings. While the underlying comorbidities of a patient significantly contributes to their susceptibility to and outcome following SAB, recent studies show the importance of the level of cytolytic toxin production by the infecting bacterium. In this study we demonstrate that this cytotoxicity can be determined directly from the diagnostic MALDI-TOF mass spectrum generated in a routine diagnostic laboratory. With further development this information could be used to guide the management and improve the outcomes for SAB patients.",,doi:https://doi.org/10.1099/mic.0.001223; html:https://europepmc.org/articles/PMC10323763; pdf:https://europepmc.org/articles/PMC10323763?pdf=render 32626822,https://doi.org/10.1007/s41109-020-00273-3,Normalised degree variance.,"Smith KM, Escudero J.",,Applied network science,2020,2020-06-22,Y,,,,"Finding graph indices which are unbiased to network size and density is of high importance both within a given field and across fields for enhancing comparability of modern network science studies. The degree variance is an important metric for characterising network degree heterogeneity. Here, we provide an analytically valid normalisation of degree variance to replace previous normalisations which are either invalid or not applicable to all networks. It is shown that this normalisation provides equal values for graphs and their complements; it is maximal in the star graph (and its complement); and its expected value is constant with respect to density for Erdös-Rényi (ER) random graphs of the same size. We strengthen these results with model observations in ER random graphs, random geometric graphs, scale-free networks, random hierarchy networks and resting-state brain networks, showing that the proposed normalisation is generally less affected by both network size and density than previous normalisation attempts. The closed form expression proposed also benefits from high computational efficiency and straightforward mathematical analysis. Analysis of 184 real-world binary networks across different disciplines shows that normalised degree variance is not correlated with average degree and is robust to node and edge subsampling. Comparisons across subdomains of biological networks reveals greater degree heterogeneity among brain connectomes and food webs than in protein interaction networks.",,doi:https://doi.org/10.1007/s41109-020-00273-3; html:https://europepmc.org/articles/PMC7319291; pdf:https://europepmc.org/articles/PMC7319291?pdf=render 34605164,https://doi.org/10.1002/mnfr.202100316,Odd Chain Fatty Acids Are Not Robust Biomarkers for Dietary Intake of Fiber.,"Wu Y, Posma JM, Holmes E, Frost G, Chambers ES, Garcia-Perez I.",,Molecular nutrition & food research,2021,2021-10-22,N,dietary fiber; Short Chain Fatty Acids; Biomarker Validation; Dietary Biomarker; Odd Chain Fatty Acids,,,"

Scope

Prior investigation has suggested a positive association between increased colonic propionate production and circulating odd-chain fatty acids (OCFAs; pentadecanoic acid [C15:0], heptadecanoic acid [C17:0]). As the major source of propionate in humans is the microbial fermentation of dietary fiber, OCFAs have been proposed as candidate biomarkers of dietary fiber. The objective of this study is to critically assess the plausibility, robustness, reliability, dose-response, time-response aspects of OCFAs as potential biomarkers of fermentable fibers in two independent studies using a validated analytical method.

Methods and results

OCFAs are first assessed in a fiber supplementation study, where 21 participants received 10 g dietary fiber supplementation for 7 days. OCFAs are then assessed in a highly controlled inpatient setting, which 19 participants consumed a high fiber (45.1 g per day) and a low fiber diet (13.6 g per day) for 4 days. Collectively in both studies, dietary intakes of fiber as fiber supplementations or having consumed a high fiber diet do not increase circulating levels of OCFAs. The dose and temporal relations are not observed.

Conclusion

Current study has generated new insight on the utility of OCFAs as fiber biomarkers and highlighted the importance of critical assessment of candidate biomarkers before application.",,doi:https://doi.org/10.1002/mnfr.202100316; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mnfr.202100316 -37489768,https://doi.org/10.1161/jaha.122.029296,Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.,"Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.",,Journal of the American Heart Association,2023,2023-07-25,Y,Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records,,,"Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.",,doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296 33280008,https://doi.org/10.1093/cercor/bhaa345,Hierarchical Complexity of the Macro-Scale Neonatal Brain.,"Blesa M, Galdi P, Cox SR, Sullivan G, Stoye DQ, Lamb GJ, Quigley AJ, Thrippleton MJ, Escudero J, Bastin ME, Smith KM, Boardman JP.",,"Cerebral cortex (New York, N.Y. : 1991)",2021,2021-03-01,Y,Newborn; Network Analysis; Developing Brain; Dmri; Structural Connectome; Hierarchical Complexity,,,"The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.",,doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render +37489768,https://doi.org/10.1161/jaha.122.029296,Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.,"Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.",,Journal of the American Heart Association,2023,2023-07-25,Y,Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records,,,"Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.",,doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296 35640889,https://doi.org/10.1093/ehjci/jeac101,Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.,"Ardissino M, McCracken C, Bard A, Antoniades C, Neubauer S, Harvey NC, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2022,2022-10-01,Y,Arterial stiffness; Cardiovascular Magnetic Resonance; Left ventricle; Pericardial Fat; Left Atrium; Cardiometabolic Disease,,,"

Aims

We evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying mechanism in 42 598 UK Biobank participants.

Methods and results

We extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships.

Conclusion

We demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk.",,doi:https://doi.org/10.1093/ehjci/jeac101; html:https://europepmc.org/articles/PMC9584621; pdf:https://europepmc.org/articles/PMC9584621?pdf=render 34819519,https://doi.org/10.1038/s41467-021-27164-0,Synergistic insights into human health from aptamer- and antibody-based proteomic profiling.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Kerrison ND, Oerton E, Koprulu M, Luan J, Hingorani AD, Williams SA, Wareham NJ, Langenberg C.",,Nature communications,2021,2021-11-24,Y,,,,"Affinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques-the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays-to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein-phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer's disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.",,doi:https://doi.org/10.1038/s41467-021-27164-0; html:https://europepmc.org/articles/PMC8613205; pdf:https://europepmc.org/articles/PMC8613205?pdf=render 30984881,https://doi.org/10.12688/wellcomeopenres.15151.1,Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England.,"Aldridge RW, Menezes D, Lewer D, Cornes M, Evans H, Blackburn RM, Byng R, Clark M, Denaxas S, Fuller J, Hewett N, Kilmister A, Luchenski S, Manthorpe J, McKee M, Neale J, Story A, Tinelli M, Whiteford M, Wurie F, Hayward A.",,Wellcome open research,2019,2019-03-11,Y,Mortality; Data Linkage; Hospital Discharge; Amenable Mortality; Homeless Health; Homeless Healthcare,,,"Background: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes.  Methods: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group). Results: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0).  The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600).  The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512). Conclusion: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions.",,doi:https://doi.org/10.12688/wellcomeopenres.15151.1; html:https://europepmc.org/articles/PMC6449792; pdf:https://europepmc.org/articles/PMC6449792?pdf=render @@ -781,21 +784,21 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 32398093,https://doi.org/10.1186/s13063-020-04329-8,Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.,"Lensen S, Macnair A, Love SB, Yorke-Edwards V, Noor NM, Martyn M, Blenkinsop A, Diaz-Montana C, Powell G, Williamson E, Carpenter J, Sydes MR.",,Trials,2020,2020-05-12,Y,Systematic review; Rct; Registry; Routinely Collected Health Data,,,"

Background

Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.

Methods

We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019.

Results

We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.

Conclusions

In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities.

Trial registration

PROSPERO CRD42019123088.",,doi:https://doi.org/10.1186/s13063-020-04329-8; html:https://europepmc.org/articles/PMC7218527; pdf:https://europepmc.org/articles/PMC7218527?pdf=render 35463778,https://doi.org/10.3389/fcvm.2022.859310,Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-Based Segmentation.,"Puyol-Antón E, Ruijsink B, Mariscal Harana J, Piechnik SK, Neubauer S, Petersen SE, Razavi R, Chowienczyk P, King AP.",,Frontiers in cardiovascular medicine,2022,2022-04-07,Y,Segmentation; Cardiac Magnetic Resonance; Deep Learning; Fair Ai; Inequality Fairness In Deep Learning-Based Cmr Segmentation,,,"

Background

Artificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias. The objective of this paper is to perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.

Methods

A state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5 ± 7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.

Results

Results on the overall population showed an excellent agreement between the manual and automatic segmentations. We found statistically significant differences in Dice scores between races (white ∼94% vs. minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders. The results of a multivariate linear regression analysis showed that no covariate could explain the Dice score bias between racial groups. However, for the Mixed and Black race groups, sex showed a weak positive association with the Dice score. The results of an ANCOVA analysis showed that race was the main factor that can explain the overall difference in Dice scores between racial groups.

Conclusion

We have shown that racial bias can exist in DL-based cine CMR segmentation models when training with a database that is sex-balanced but not race-balanced such as the UK Biobank.",,doi:https://doi.org/10.3389/fcvm.2022.859310; html:https://europepmc.org/articles/PMC9021445; pdf:https://europepmc.org/articles/PMC9021445?pdf=render 36538350,https://doi.org/10.2196/41200,Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.,"MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.",,JMIR medical informatics,2022,2022-12-20,Y,Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride,,,"

Background

Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.

Objective

This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).

Results

Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).

Conclusions

Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.",,doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268 -37606853,https://doi.org/10.1007/s00520-023-07944-8,"The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.","Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-08-22,Y,Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic,,,"

Purpose

Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods

A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Results

We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.

Conclusions

We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.",,doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf -35870544,https://doi.org/10.1016/j.cpcardiol.2022.101330,Artificial Intelligence and Cardiovascular Magnetic Resonance Imaging in Myocardial Infarction Patients.,"Chong JH, Abdulkareem M, Petersen SE, Khanji MY.",,Current problems in cardiology,2022,2022-07-21,N,,,,"Cardiovascular magnetic resonance (CMR) is an important cardiac imaging tool for assessing the prognostic extent of myocardial injury after myocardial infarction (MI). Within the context of clinical trials, CMR is also useful for assessing the efficacy of potential cardioprotective therapies in reducing MI size and preventing adverse left ventricular (LV) remodelling in reperfused MI. However, manual contouring and analysis can be time-consuming with interobserver and intra-observer variability, which can in turn lead to reduction in accuracy and precision of analysis. There is thus a need to automate CMR scan analysis in MI patients to save time, increase accuracy, increase reproducibility and increase precision. In this regard, automated imaging analysis techniques based on artificial intelligence (AI) that are developed with machine learning (ML), and more specifically deep learning (DL) strategies, can enable efficient, robust, accurate and clinician-friendly tools to be built so as to try and improve both clinician productivity and quality of patient care. In this review, we discuss basic concepts of ML in CMR, important prognostic CMR imaging biomarkers in MI and the utility of current ML applications in their analysis as assessed in research studies. We highlight potential barriers to the mainstream implementation of these automated strategies and discuss related governance and quality control issues. Lastly, we discuss the future role of ML applications in clinical trials and the need for global collaboration in growing this field.",,doi:https://doi.org/10.1016/j.cpcardiol.2022.101330 32616677,https://doi.org/10.1212/wnl.0000000000009924,Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.,"Rannikmäe K, Ngoh K, Bush K, Al-Shahi Salman R, Doubal F, Flaig R, Henshall DE, Hutchison A, Nolan J, Osborne S, Samarasekera N, Schnier C, Whiteley W, Wilkinson T, Wilson K, Woodfield R, Zhang Q, Allen N, Sudlow CLM.",,Neurology,2020,2020-07-02,Y,,,,"

Objective

In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes.

Methods

In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type.

Results

Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise.

Conclusions

Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.",,doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render +35870544,https://doi.org/10.1016/j.cpcardiol.2022.101330,Artificial Intelligence and Cardiovascular Magnetic Resonance Imaging in Myocardial Infarction Patients.,"Chong JH, Abdulkareem M, Petersen SE, Khanji MY.",,Current problems in cardiology,2022,2022-07-21,N,,,,"Cardiovascular magnetic resonance (CMR) is an important cardiac imaging tool for assessing the prognostic extent of myocardial injury after myocardial infarction (MI). Within the context of clinical trials, CMR is also useful for assessing the efficacy of potential cardioprotective therapies in reducing MI size and preventing adverse left ventricular (LV) remodelling in reperfused MI. However, manual contouring and analysis can be time-consuming with interobserver and intra-observer variability, which can in turn lead to reduction in accuracy and precision of analysis. There is thus a need to automate CMR scan analysis in MI patients to save time, increase accuracy, increase reproducibility and increase precision. In this regard, automated imaging analysis techniques based on artificial intelligence (AI) that are developed with machine learning (ML), and more specifically deep learning (DL) strategies, can enable efficient, robust, accurate and clinician-friendly tools to be built so as to try and improve both clinician productivity and quality of patient care. In this review, we discuss basic concepts of ML in CMR, important prognostic CMR imaging biomarkers in MI and the utility of current ML applications in their analysis as assessed in research studies. We highlight potential barriers to the mainstream implementation of these automated strategies and discuss related governance and quality control issues. Lastly, we discuss the future role of ML applications in clinical trials and the need for global collaboration in growing this field.",,doi:https://doi.org/10.1016/j.cpcardiol.2022.101330 +37606853,https://doi.org/10.1007/s00520-023-07944-8,"The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.","Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-08-22,Y,Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic,,,"

Purpose

Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods

A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Results

We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.

Conclusions

We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.",,doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf 32926504,https://doi.org/10.1002/pds.5121,Implementing high-dimensional propensity score principles to improve confounder adjustment in UK electronic health records.,"Tazare J, Smeeth L, Evans SJW, Williamson E, Douglas IJ.",,Pharmacoepidemiology and drug safety,2020,2020-09-14,N,Pharmacoepidemiology; Electronic Health Records; Electronic Medical Records; High-dimensional Propensity Score; Database Research; Confounder Adjustment,,,"

Purpose

Recent evidence from US claims data suggests use of high-dimensional propensity score (hd-PS) methods improve adjustment for confounding in non-randomised studies of interventions. However, it is unclear how best to apply hd-PS principles outside their original setting, given important differences between claims data and electronic health records (EHRs). We aimed to implement the hd-PS in the setting of United Kingdom (UK) EHRs.

Methods

We studied the interaction between clopidogrel and proton pump inhibitors (PPIs). Whilst previous observational studies suggested an interaction (with reduced effect of clopidogrel), case-only, genetic and randomised trial approaches showed no interaction, strongly suggesting the original observational findings were subject to confounding. We derived a cohort of clopidogrel users from the UK Clinical Practice Research Datalink linked with the Myocardial Ischaemia National Audit Project. Analyses estimated the hazard ratio (HR) for myocardial infarction (MI) comparing PPI users with non-users using a Cox model adjusting for confounders. To reflect unique characteristics of UK EHRs, we varied the application of hd-PS principles including the level of grouping within coding systems and adapting the assessment of code recurrence. Results were compared with traditional analyses.

Results

Twenty-four thousand four hundred and seventy-one patients took clopidogrel, of whom 9111 were prescribed a PPI. Traditional PS approaches obtained a HR for the association between PPI use and MI of 1.17 (95% CI: 1.00-1.35). Applying hd-PS modifications resulted in estimates closer to the expected null (HR 1.00; 95% CI: 0.78-1.28).

Conclusions

hd-PS provided improved adjustment for confounding compared with other approaches, suggesting hd-PS can be usefully applied in UK EHRs.",,doi:https://doi.org/10.1002/pds.5121 36439548,https://doi.org/10.3389/fsurg.2022.870494,Development and validation of an automated basal cell carcinoma histopathology information extraction system using natural language processing.,"Ali SR, Strafford H, Dobbs TD, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,Frontiers in surgery,2022,2022-08-24,Y,Electronic Health Records (Ehrs); Natural Language Processing (Nlp); Basal Cell Carcinoma (Bcc); Non-melanoma Skin Cancer (Nmsc); Information Extraction (Ie),,,"

Introduction

Routinely collected healthcare data are a powerful research resource, but often lack detailed disease-specific information that is collected in clinical free text such as histopathology reports. We aim to use natural Language Processing (NLP) techniques to extract detailed clinical and pathological information from histopathology reports to enrich routinely collected data.

Methods

We used the general architecture for text engineering (GATE) framework to build an NLP information extraction system using rule-based techniques. During validation, we deployed our rule-based NLP pipeline on 200 previously unseen, de-identified and pseudonymised basal cell carcinoma (BCC) histopathological reports from Swansea Bay University Health Board, Wales, UK. The results of our algorithm were compared with gold standard human annotation by two independent and blinded expert clinicians involved in skin cancer care.

Results

We identified 11,224 items of information with a mean precision, recall, and F1 score of 86.0% (95% CI: 75.1-96.9), 84.2% (95% CI: 72.8-96.1), and 84.5% (95% CI: 73.0-95.1), respectively. The difference between clinician annotator F1 scores was 7.9% in comparison with 15.5% between the NLP pipeline and the gold standard corpus. Cohen's Kappa score on annotated tokens was 0.85.

Conclusion

Using an NLP rule-based approach for named entity recognition in BCC, we have been able to develop and validate a pipeline with a potential application in improving the quality of cancer registry data, supporting service planning, and enhancing the quality of routinely collected data for research.",,doi:https://doi.org/10.3389/fsurg.2022.870494; html:https://europepmc.org/articles/PMC9683031; pdf:https://europepmc.org/articles/PMC9683031?pdf=render 33306026,https://doi.org/10.2196/23369,Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.,"Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.",,Journal of medical Internet research,2020,2020-12-11,Y,Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations,,,"

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.",,doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688 +32460529,https://doi.org/10.1161/circimaging.119.010389,Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.,"Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.",,Circulation. Cardiovascular imaging,2020,2020-05-28,N,Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis,,,,,doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389 36864090,https://doi.org/10.1038/s41598-023-30369-6,Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes. ,"Hemerich D, Smit RAJ, Preuss M, Stalbow L, van der Laan SW, Asselbergs FW, van Setten J, Tragante V.",,Scientific reports,2023,2023-03-02,Y,,,,"Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression. We searched for T2D-associated variants acting on regulatory elements and expression quantitative trait loci (eQTLs) in nine tissues. We used T2D tissue-grouped variant sets as genetic instruments to conduct 2-Sample Mendelian Randomization (MR) in ten related outcomes whose risk is increased by T2D using the FinnGen cohort. We performed PheWAS analysis to investigate whether the T2D tissue-grouped variant sets had specific predicted disease signatures. We identified an average of 176 variants acting in nine tissues implicated in T2D, and an average of 30 variants acting on regulatory elements that are unique to the nine tissues of interest. In 2-Sample MR analyses, all subsets of regulatory variants acting in different tissues were associated with increased risk of the ten secondary outcomes studied on similar levels. No tissue-grouped variant set was associated with an outcome significantly more than other tissue-grouped variant sets. We did not identify different disease progression profiles based on tissue-specific regulatory and transcriptome information. Bigger sample sizes and other layers of regulatory information in critical tissues may help identify subsets of T2D variants that are implicated in certain secondary outcomes, uncovering system-specific disease progression.",,doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render 37143831,https://doi.org/10.1183/23120541.00591-2022,Ethnic variation in asthma healthcare utilisation and exacerbation: systematic review and meta-analysis.,"Akin-Imran A, Bajpai A, McCartan D, Heaney LG, Kee F, Redmond C, Busby J.",,ERJ open research,2023,2023-05-02,Y,,,,"

Background

Patients from ethnic minority groups (EMGs) frequently report poorer asthma outcomes; however, a broad synthesis summarising ethnic disparities is yet to be undertaken. What is the magnitude of ethnic disparities in asthma healthcare utilisation, exacerbations and mortality?

Methods

MEDLINE, Embase and Web of Science databases were searched for studies reporting ethnic variation in asthma healthcare outcomes (primary care attendance, exacerbation, emergency department (ED) visits, hospitalisation, hospital readmission, ventilation/intubation and mortality) between White patients and those from EMGs. Estimates were displayed using forest plots and random-effects models were used to calculate pooled estimates. We conducted subgroup analyses to explore heterogeneity, including by specific ethnicity (Black, Hispanic, Asian and other).

Results

65 studies, comprising 699 882 patients, were included. Most studies (92.3%) were conducted in the United States of America (USA). Patients from EMGs had evidence suggestive of lower levels of primary care attendance (OR 0.72, 95% CI 0.48-1.09), but substantially higher ED visits (OR 1.74, 95% CI 1.53-1.98), hospitalisations (OR 1.63, 95% CI 1.48-1.79) and ventilation/intubation (OR 2.67, 95% CI 1.65-4.31) when compared to White patients. In addition, we found evidence suggestive of increased hospital readmissions (OR 1.19, 95% CI 0.90-1.57) and exacerbation rates (OR 1.10, 95% CI 0.94-1.28) among EMGs. No eligible studies explored disparities in mortality. ED visits were much higher among Black and Hispanic patients, while Asian and other ethnicities had similar rates to White patients.

Conclusions

EMGs had higher secondary care utilisation and exacerbations. Despite the global importance of this issue, the majority of studies were performed in the USA. Further research into the causes of these disparities, including whether these vary by specific ethnicity, is required to aid the design of effective interventions.",,doi:https://doi.org/10.1183/23120541.00591-2022; html:https://europepmc.org/articles/PMC10152257; pdf:https://europepmc.org/articles/PMC10152257?pdf=render -32460529,https://doi.org/10.1161/circimaging.119.010389,Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.,"Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.",,Circulation. Cardiovascular imaging,2020,2020-05-28,N,Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis,,,,,doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389 33147524,https://doi.org/10.1016/j.puhe.2020.08.027,Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study.,"Evans A, Hardcastle K, Bandyopadhyay A, Farewell D, John A, Lyons RA, Long S, Bellis MA, Paranjothy S.",,Public health,2020,2020-11-02,N,Social Inequalities; Adverse Childhood Experiences; Education Outcomes,,,"

Objectives

Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years.

Study design

The study design used in the study is a population-based electronic cohort study.

Methods

We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors.

Results

There were 107,479 and 43,648 children included in the analysis, with follow-up to 6-7 years (KS1) and 10-11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09-1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10-1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37-1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04-1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84-2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment.

Conclusion

The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation.",,doi:https://doi.org/10.1016/j.puhe.2020.08.027 36936265,https://doi.org/10.1136/bmjmed-2022-000276,"Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.","Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",,BMJ medicine,2023,2023-01-13,Y,Therapeutics; Community health services; Public Health; Covid-19,,,"

Objective

To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.

Design

Retrospective, descriptive cohort study, approved by NHS England.

Setting

Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.

Participants

Outpatients with covid-19 at high risk of severe outcomes.

Interventions

Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.

Results

93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).

Conclusions

Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.",,doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render; pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf -36197964,https://doi.org/10.1126/scitranslmed.abq4810,"Comment on ""A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk"".","Kivimäki M, Hingorani AD, Lindbohm JV.",,Science translational medicine,2022,2022-10-05,N,,,,"A 27-protein signature has been proposed to predict cardiovascular disease, but its applicability in clinical decision-making remains unclear.",,doi:https://doi.org/10.1126/scitranslmed.abq4810 30240446,https://doi.org/10.1371/journal.pone.0203896,Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts.,"Ward J, Graham N, Strawbridge RJ, Ferguson A, Jenkins G, Chen W, Hodgson K, Frye M, Weinshilboum R, Uher R, Lewis CM, Biernacka J, Smith DJ.",,PloS one,2018,2018-09-21,Y,,Better Care,,"There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.",,doi:https://doi.org/10.1371/journal.pone.0203896; html:https://europepmc.org/articles/PMC6150505; pdf:https://europepmc.org/articles/PMC6150505?pdf=render -37505992,https://doi.org/10.1093/ageing/afad136,The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.,"Cheong VL, Mehdizadeh D, Todd OM, Gardner P, Zaman H, Clegg A, Alldred DP, Faisal M.",,Age and ageing,2023,2023-07-01,Y,Frailty; Older People; Older Adults; Routine Data; Anticholinergic Burden; Structured Medication Review,,,"

Background

Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status.

Methods

Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum).

Results

In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)).

Conclusions

Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.",,doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf +36197964,https://doi.org/10.1126/scitranslmed.abq4810,"Comment on ""A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk"".","Kivimäki M, Hingorani AD, Lindbohm JV.",,Science translational medicine,2022,2022-10-05,N,,,,"A 27-protein signature has been proposed to predict cardiovascular disease, but its applicability in clinical decision-making remains unclear.",,doi:https://doi.org/10.1126/scitranslmed.abq4810 32788201,https://doi.org/10.1136/archdischild-2020-319027,Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis.,"Syed S, Ashwick R, Schlosser M, Gonzalez-Izquierdo A, Li L, Gilbert R.",,Archives of disease in childhood,2021,2020-08-11,Y,Data collection; epidemiology; Child Abuse; Health Services Research; Drug Withdrawal,,,"

Objective

Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

Methods

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. We pooled PPVs for each indicator using random effects meta-analyses.

Results

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs: 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Conclusions

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.",,doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render +37505992,https://doi.org/10.1093/ageing/afad136,The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.,"Cheong VL, Mehdizadeh D, Todd OM, Gardner P, Zaman H, Clegg A, Alldred DP, Faisal M.",,Age and ageing,2023,2023-07-01,Y,Frailty; Older People; Older Adults; Routine Data; Anticholinergic Burden; Structured Medication Review,,,"

Background

Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status.

Methods

Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum).

Results

In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)).

Conclusions

Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.",,doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf 37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render 34649961,https://doi.org/10.1101/cshperspect.a039230,Human Genomics and Drug Development.,"Schmidt AF, Hingorani AD, Finan C.",,Cold Spring Harbor perspectives in medicine,2022,2022-02-01,N,,,,"Insights into the genetic basis of human disease are helping to address some of the key challenges in new drug development including the very high rates of failure. Here we review the recent history of an emerging, genomics-assisted approach to pharmaceutical research and development, and its relationship to Mendelian randomization (MR), a well-established analytical approach to causal inference. We demonstrate how human genomic data linked to pharmaceutically relevant phenotypes can be used for (1) drug target identification (mapping relevant drug targets to diseases), (2) drug target validation (inferring the likely effects of drug target perturbation), (3) evaluation of the effectiveness and specificity of compound-target engagement (inferring the extent to which the effects of a compound are exclusive to the target and distinguishing between on-target and off-target compound effects), and (4) the selection of end points in clinical trials (the diseases or conditions to be evaluated as trial outcomes). We show how genomics can help identify indication expansion opportunities for licensed drugs and repurposing of compounds developed to clinical phase that proved safe but ineffective for the original intended indication. We outline statistical and biological considerations in using MR for drug target validation (drug target MR) and discuss the obstacles and challenges for scaled applications of these genomics-based approaches.",,doi:https://doi.org/10.1101/cshperspect.a039230 36333542,https://doi.org/10.1007/s10654-022-00934-w,Biases arising from linked administrative data for epidemiological research: a conceptual framework from registration to analyses.,"Shaw RJ, Harron KL, Pescarini JM, Pinto Junior EP, Allik M, Siroky AN, Campbell D, Dundas R, Ichihara MY, Leyland AH, Barreto ML, Katikireddi SV.",,European journal of epidemiology,2022,2022-11-05,Y,Data Linkage; Record Linkage; Administrative Data; Epidemiological Biases; Linkage Error,,,"Linked administrative data offer a rich source of information that can be harnessed to describe patterns of disease, understand their causes and evaluate interventions. However, administrative data are primarily collected for operational reasons such as recording vital events for legal purposes, and planning, provision and monitoring of services. The processes involved in generating and linking administrative datasets may generate sources of bias that are often not adequately considered by researchers. We provide a framework describing these biases, drawing on our experiences of using the 100 Million Brazilian Cohort (100MCohort) which contains records of more than 131 million people whose families applied for social assistance between 2001 and 2018. Datasets for epidemiological research were derived by linking the 100MCohort to health-related databases such as the Mortality Information System and the Hospital Information System. Using the framework, we demonstrate how selection and misclassification biases may be introduced in three different stages: registering and recording of people's life events and use of services, linkage across administrative databases, and cleaning and coding of variables from derived datasets. Finally, we suggest eight recommendations which may reduce biases when analysing data from administrative sources.",,doi:https://doi.org/10.1007/s10654-022-00934-w; html:https://europepmc.org/articles/PMC9792414; pdf:https://europepmc.org/articles/PMC9792414?pdf=render @@ -810,32 +813,32 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 33851963,https://doi.org/10.1001/jamadermatol.2021.0009,Association Between Atopic Dermatitis and Educational Attainment in Denmark. ,"Schmidt SAJ, Mailhac A, Darvalics B, Mulick A, Deleuran MS, Sørensen HT, Riis JL, Langan SM.",,JAMA dermatology,2021,2021-04-14,Y,,,,"Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance. To examine whether a childhood diagnosis of AD is associated with lower educational attainment. This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021. Hospital-diagnosed AD. Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age. The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]). This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.",,doi:https://doi.org/10.1001/jamadermatol.2021.0009; html:https://europepmc.org/articles/PMC8047754 34673925,https://doi.org/10.1093/ageing/afab201,"Do home adaptation interventions help to reduce emergency fall admissions? A national longitudinal data-linkage study of 657,536 older adults living in Wales (UK) between 2010 and 2017. ","Hollinghurst J, Daniels H, Fry R, Akbari A, Rodgers S, Watkins A, Hillcoat-Nallétamby S, Williams N, Nikolova S, Meads D, Clegg A.",,Age and ageing,2022,2022-01-01,Y,,,,"falls are common in older people, but evidence for the effectiveness of preventative home adaptations is limited. determine whether a national home adaptation service, Care&Repair Cymru (C&RC), identified individuals at risk of falls occurring at home and reduced the likelihood of falls. retrospective longitudinal controlled non-randomised intervention cohort study. our cohort consisted of 657,536 individuals aged 60+ living in Wales (UK) between 1 January 2010 and 31 December 2017. About 123,729 individuals received a home adaptation service. we created a dataset with up to 41 quarterly observations per person. For each quarter, we observed if a fall occurred at home that resulted in either an emergency department or an emergency hospital admission. We analysed the data using multilevel logistic regression. compared to the control group, C&RC clients had higher odds of falling, with an odds ratio (OR [95% confidence interval]) of 1.93 [1.87, 2.00]. Falls odds was higher for females (1.44 [1.42, 1.46]), older age (1.07 [1.07, 1.07]), increased frailty (mild 1.57 [1.55, 1.60], moderate 2.31 [2.26, 2.35], severe 3.05 [2.96, 3.13]), and deprivation (most deprived compared to least: 1.16 [1.13, 1.19]). Client fall odds decreased post-intervention; OR 0.97 [0.96, 0.97] per quarter. Regional variation existed for falls (5.8%), with most variation at the individual level (31.3%). C&RC identified people more likely to have an emergency fall admission occurring at home, and their service reduced the odds of falling post-intervention. Service provisioning should meet the needs of an individual and need varies by personal and regional circumstance.",,doi:https://doi.org/10.1093/ageing/afab201; html:https://europepmc.org/articles/PMC8753038; pdf:https://europepmc.org/articles/PMC8753038?pdf=render 36644660,https://doi.org/10.1177/20552076221128677,Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.,"Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",,Digital health,2023,2023-01-08,Y,Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health,,,"The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",,doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render -36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/S2589-7500(22)00151-0; doi:https://doi.org/10.1016/s2589-7500(22)00151-0 34564897,https://doi.org/10.1002/gps.5627,Living well with dementia: What is possible and how to promote it.,"Quinn C, Pickett JA, Litherland R, Morris RG, Martyr A, Clare L, On behalf of the IDEAL Programme Team.",,International journal of geriatric psychiatry,2022,2021-10-13,Y,Quality of life; Alzheimer's; Well-being; Carer; Post-diagnostic Support,,,,,doi:https://doi.org/10.1002/gps.5627; html:https://europepmc.org/articles/PMC9292841; pdf:https://europepmc.org/articles/PMC9292841?pdf=render +36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/S2589-7500(22)00151-0; doi:https://doi.org/10.1016/s2589-7500(22)00151-0 37440761,https://doi.org/10.1093/ehjci/jead166,Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.,"Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-07-13,N,,,,"

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36,309 UK Biobank participants (average age= 63.9±7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.",,doi:https://doi.org/10.1093/ehjci/jead166; pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf 35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render 35698725,https://doi.org/10.1016/s2665-9913(22)00098-4,Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.,"MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",,The Lancet. Rheumatology,2022,2022-06-09,Y,,,,"

Background

The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.

Methods

We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).

Findings

We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49).

Interpretation

COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.

Funding

UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",,doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render 37395705,https://doi.org/10.1167/tvst.12.7.3,Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.,"Courtie EF, Gilani A, Capewell N, Kale AU, Hui BTK, Liu X, Montesano G, Teussink M, Denniston AK, Veenith T, Blanch RJ.",,Translational vision science & technology,2023,2023-07-01,Y,,,,"

Purpose

Investigate the association between the optical coherence tomography angiography (OCTA) metrics derived from different analysis programs to understand the comparability of studies using these different approaches.

Methods

Secondary analysis of a prospective observational study (March 2018-September 2021). Forty-four right eyes and 42 left eyes from 44 patients were included. Patients were either undergoing upper gastrointestinal surgery with a critical care stay planned or were already in the critical care unit with sepsis. OCTA scans were obtained in an ophthalmology department or critical care setting. Fourteen OCTA metrics were compared within and between the programs, and agreement was measured by Pearson's R coefficient and intraclass correlation coefficient.

Results

Correlation was highest between all Heidelberg metrics and Fractalyse (all >0.84), and lowest between Matlab skeletonized or foveal avascular zone metrics and all other measures (e.g., skeletal fractal dimension and vessel density at -0.02). Agreement between eyes was moderate to excellent in all metrics (0.60-0.90).

Conclusions

The significant variability between metrics and programs used for OCTA analysis demonstrates that they are not interchangeable and supports a recommendation for perfusion density metrics to be reported as standard.

Translational relevance

Agreement between different OCTA analyses is variable and not interchangeable. The high agreement between non-skeletonized vessel density metrics suggests that these should be routinely reported.",,doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render 33497994,https://doi.org/10.1016/j.puhe.2020.12.003,Obesity during the COVID-19 pandemic: both cause of high risk and potential effect of lockdown? A population-based electronic health record study.,"Katsoulis M, Pasea L, Lai AG, Dobson RJB, Denaxas S, Hemingway H, Banerjee A.",,Public health,2021,2020-12-14,Y,Obesity; Diabetes; Coronavirus; Physical Activity; cardiovascular,,,"

Objectives

Obesity is a modifiable risk factor for coronavirus disease 2019 (COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in health care, and also due to potential increasing obesity during lockdown.

Study design

The study design of this study is a retrospective cohort study and causal inference methods.

Methods

In population-based electronic health records for 1,958,638 individuals in England, we estimated 1-year mortality risk ('direct' and 'indirect' effects) for obese individuals, incorporating (i) pre-COVID-19 risk by age, sex and comorbidities, (ii) population infection rate and (iii) relative impact on mortality (relative risk [RR]: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body mass index (BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions (cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and chronic kidney disease), accounting for confounders.

Results

For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0, respectively, and indirect effect of 383-767 excess deaths, assuming 40% and 80% will be affected at RR = 1.2. Owing to BMI change during the lockdown, we estimated that 97,755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434,104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) would be at higher risk for COVID-19 over one year.

Conclusions

Prevention of obesity and promotion of physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.",,doi:https://doi.org/10.1016/j.puhe.2020.12.003; html:https://europepmc.org/articles/PMC7832229; pdf:https://europepmc.org/articles/PMC7832229?pdf=render 31104603,https://doi.org/10.1098/rstb.2018.0276,Outbreak analytics: a developing data science for informing the response to emerging pathogens.,"Polonsky JA, Baidjoe A, Kamvar ZN, Cori A, Durski K, Edmunds WJ, Eggo RM, Funk S, Kaiser L, Keating P, de Waroux OLP, Marks M, Moraga P, Morgan O, Nouvellet P, Ratnayake R, Roberts CH, Whitworth J, Jombart T.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2019,2019-07-01,Y,Methods; Software; epidemics; Infectious; pipeline; Tools,Applied Analytics,,"Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise of outbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.",,doi:https://doi.org/10.1098/rstb.2018.0276; html:https://europepmc.org/articles/PMC6558557; pdf:https://europepmc.org/articles/PMC6558557?pdf=render; pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2018.0276 -37337639,https://doi.org/10.1002/ctm2.1291,Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.,"Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.",,Clinical and translational medicine,2023,2023-06-01,Y,Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic,,,"

Background

While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.

Methods

The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.

Results

We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.

Conclusions

Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.",,doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render 33516523,https://doi.org/10.1016/j.jaci.2020.12.001,"Atopic eczema in adulthood and mortality: UK population-based cohort study, 1998-2016.","Silverwood RJ, Mansfield KE, Mulick A, Wong AYS, Schmidt SAJ, Roberts A, Smeeth L, Abuabara K, Langan SM.",,The Journal of allergy and clinical immunology,2021,2021-01-27,Y,Activity; Mortality; Cohort study; United Kingdom; Primary Care; Atopic Eczema; Severity; Population-based; Electronic Health Care Records,,,"

Background

Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death.

Objective

We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity.

Methods

The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016.

Results

A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes.

Conclusion

The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority.",,doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render +37337639,https://doi.org/10.1002/ctm2.1291,Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.,"Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.",,Clinical and translational medicine,2023,2023-06-01,Y,Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic,,,"

Background

While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.

Methods

The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.

Results

We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.

Conclusions

Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.",,doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render 31685485,https://doi.org/10.1136/bmjopen-2019-031365,"Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison.","Demmler JC, Atkinson MD, Reinhold EJ, Choy E, Lyons RA, Brophy ST.",,BMJ open,2019,2019-11-04,Y,Prevalence; Joint Hypermobility Syndrome; Ehlers-danlos Syndromes; Heritable Disorders Of Connective Tissue; Hypermobility Spectrum Disorder; Health Data Linkage,Improving Public Health,,"

Objectives

To describe the epidemiology of diagnosed hypermobility spectrum disorder (HSD) and Ehlers-Danlos syndromes (EDS) using linked electronic medical records. To examine whether these conditions remain rare and primarily affect the musculoskeletal system.

Design

Nationwide linked electronic cohort and nested case-control study.

Setting

Routinely collected data from primary care and hospital admissions in Wales, UK.

Participants

People within the primary care or hospital data systems with a coded diagnosis of EDS or joint hypermobility syndrome (JHS) between 1 July 1990 and 30 June 2017.

Main outcome measures

Combined prevalence of JHS and EDS in Wales. Additional diagnosis and prescription data in those diagnosed with EDS or JHS compared with matched controls.

Results

We found 6021 individuals (men: 30%, women: 70%) with a diagnostic code of either EDS or JHS. This gives a diagnosed point prevalence of 194.2 per 100 000 in 2016/2017 or roughly 10 cases in a practice of 5000 patients. There was a pronounced gender difference of 8.5 years (95% CI: 7.70 to 9.22) in the mean age at diagnosis. EDS or JHS was not only associated with high odds for other musculoskeletal diagnoses and drug prescriptions but also with significantly higher odds of a diagnosis in other disease categories (eg, mental health, nervous and digestive systems) and higher odds of a prescription in most disease categories (eg, gastrointestinal and cardiovascular drugs) within the 12 months before and after the first recorded diagnosis.

Conclusions

EDS and JHS (since March 2017 classified as EDS or HSD) have historically been considered rare diseases only affecting the musculoskeletal system and soft tissues. These data demonstrate that both these assertions should be reconsidered.","epidemiological study looking at the prevalence of ehlos danlos syndrome and joint hypermobility syndrome, using SAIL database for welsh population. They found a steady increase in the rates of diagnosis for these two diseases, higher odds of being on other medication, and association with other diseases categories.",doi:https://doi.org/10.1136/bmjopen-2019-031365; html:https://europepmc.org/articles/PMC6858200; pdf:https://europepmc.org/articles/PMC6858200?pdf=render 31912053,https://doi.org/,Described Practices for Assessing Fluid Resuscitation in Acute Hospital Care: A Qualitative Study.,"Lloyd E, Ignatowicz A, Sapey E, Lasserson D, Seccombe A.",,Acute medicine,2019,2019-01-01,N,,,,"Fluid resuscitation is a widely-used treatment in acute and emergency medicine, however, the process used to perform a fluid assessment has never been studied. This qualitative study explored how acute physicians describe their approach to assessing for fluid resuscitation. 18 clinicians of varying grades consented to a semi-structured interview. Transcripts were coded and analysed using thematic analysis. Participants described three subtypes of assessment; screening assessment, emergency assessment and formal assessment. Whether a patient was 'sick' was key to determining which assessment they would receive. Marked heterogeneity was noted in the assessment processes, particularly regarding the use of history-taking. Further research is required to determine how the information gathered in these assessments is used to decide when fluid resuscitation is indicated.",, 32790708,https://doi.org/10.1371/journal.pone.0237298,Clinical academic research in the time of Corona: A simulation study in England and a call for action.,"Banerjee A, Katsoulis M, Lai AG, Pasea L, Treibel TA, Manisty C, Denaxas S, Quarta G, Hemingway H, Cavalcante JL, Noursadeghi M, Moon JC.",,PloS one,2020,2020-08-13,Y,,,,"

Objectives

We aimed to model the impact of coronavirus (COVID-19) on the clinical academic response in England, and to provide recommendations for COVID-related research.

Design

A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics).

Setting

Clinical academics in primary and secondary care in England.

Participants

Equivalent of 3200 full-time clinical academics in England.

Interventions

Four policy approaches to COVID-19 with differing population infection rates: ""Italy model"" (6%), ""mitigation"" (10%), ""relaxed mitigation"" (40%) and ""do-nothing"" (80%) scenarios. Low and high strain on the health system (no clinical academics able to do research at 10% and 5% infection rate, respectively.

Main outcome measures

Number of full-time clinical academics available to conduct clinical research during the pandemic in England.

Results

In the ""Italy model"", ""mitigation"", ""relaxed mitigation"" and ""do-nothing"" scenarios, from 5 March 2020 the duration (days) and peak infection rates (%) are 95(2.4%), 115(2.5%), 240(5.3%) and 240(16.7%) respectively. Near complete attrition of academia (87% reduction, <400 clinical academics) occurs 35 days after pandemic start for 11, 34, 62, 76 days respectively-with no clinical academics at all for 37 days in the ""do-nothing"" scenario. Restoration of normal academic workforce (80% of normal capacity) takes 11, 12, 30 and 26 weeks respectively.

Conclusions

Pandemic COVID-19 crushes the science needed at system level. National policies mitigate, but the academic community needs to adapt. We highlight six key strategies: radical prioritisation (eg 3-4 research ideas per institution), deep resourcing, non-standard leadership (repurposing of key non-frontline teams), rationalisation (profoundly simple approaches), careful site selection (eg protected sites with large academic backup) and complete suspension of academic competition with collaborative approaches.",,doi:https://doi.org/10.1371/journal.pone.0237298; html:https://europepmc.org/articles/PMC7425844; pdf:https://europepmc.org/articles/PMC7425844?pdf=render 33890864,https://doi.org/10.2196/24728,The Value of Routinely Collected Data in Evaluating Home Assessment and Modification Interventions to Prevent Falls in Older People: Systematic Literature Review. ,"Daniels H, Hollinghurst J, Fry R, Clegg A, Hillcoat-Nallétamby S, Nikolova S, Rodgers SE, Williams N, Akbari A.",,JMIR aging,2021,2021-04-23,Y,,,,"Falls in older people commonly occur at home. Home assessment and modification (HAM) interventions can be effective in reducing falls; however, there are some concerns over the validity of evaluation findings. Routinely collected data could improve the quality of HAM evaluations and strengthen their evidence base. The aim of this study is to conduct a systematic review of the evidence of the use of routinely collected data in the evaluations of HAM interventions. We searched the following databases from inception until January 31, 2020: PubMed, Ovid, CINAHL, OpenGrey, CENTRAL, LILACS, and Web of Knowledge. Eligible studies were those evaluating HAMs designed to reduce falls involving participants aged 60 years or more. We included study protocols and full reports. Bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. A total of 7 eligible studies were identified in 8 papers. Government organizations provided the majority of data across studies, with health care providers and third-sector organizations also providing data. Studies used a range of demographic, clinical and health, and administrative data. The purpose of using routinely collected data spanned recruiting and creating a sample, stratification, generating independent variables or covariates, and measuring key study-related outcomes. Nonhome-based modification interventions (eg, in nursing homes) using routinely collected data were not included in this study. We included two protocols, which meant that the results of those studies were not available. MeSH headings were excluded from the PubMed search because of a reduction in specificity. This means that some studies that met the inclusion criteria may not have been identified. Routine data can be used successfully in many aspects of HAM evaluations and can reduce biases and improve other important design considerations. However, the use of these data in these studies is currently not widespread. There are a number of governance barriers to be overcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.",,doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render -36580444,https://doi.org/10.1371/journal.pmed.1004141,Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.,"Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.",,PLoS medicine,2022,2022-12-29,Y,,,,"

Background

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

Methods and findings

The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

Conclusions

Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.",,doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render 31611193,https://doi.org/10.1136/archdischild-2019-317248,"Self-harm presentation across healthcare settings by sex in young people: an e-cohort study using routinely collected linked healthcare data in Wales, UK. ","Marchant A, Turner S, Balbuena L, Peters E, Williams D, Lloyd K, Lyons R, John A.",,Archives of disease in childhood,2020,2019-10-14,Y,,,,"This study used individual-level linked data across general practice, emergency departments (EDs), outpatients and hospital admissions to examine contacts across settings and time by sex for self-harm in individuals aged 10-24 years old in Wales, UK. A whole population-based e-cohort study of routinely collected healthcare data was conducted. Rates of self-harm across settings over time by sex were examined. Individuals were categorised based on the service(s) to which they presented. A total of 937 697 individuals aged 10-24 years contributed 5 369 794 person years of data from 1 January 2003 to 30 September 2015. Self-harm incidence was highest in primary care but remained stable over time (incident rate ratio (IRR)=1.0; 95% CI 0.9 to 1.1). Incidence of ED attendance increased over time (IRR=1.3; 95% CI 1.2 to 1.5) as did hospital admissions (IRR=1.4; 95% CI 1.1 to 1.6). Incidence in the 15-19 years age group was the highest across all settings. The largest increases were seen in the youngest age group. There were increases in ED attendances for both sexes; however, females are more likely than males to be admitted following this. This was most evident in individuals 10-15 years old, where 76% of females were admitted compared with just 49% of males. The majority of associated outpatient appointments were under a mental health specialty. This is the first study to compare self-harm in people aged 10-24 years across primary care, EDs and hospital settings in the UK. The high rates of self-harm in primary care and for young men in EDs highlight these as important settings for intervention.",,doi:https://doi.org/10.1136/archdischild-2019-317248; html:https://europepmc.org/articles/PMC7146921; pdf:https://europepmc.org/articles/PMC7146921?pdf=render +36580444,https://doi.org/10.1371/journal.pmed.1004141,Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.,"Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.",,PLoS medicine,2022,2022-12-29,Y,,,,"

Background

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

Methods and findings

The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

Conclusions

Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.",,doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render 34169636,https://doi.org/10.1002/pst.2148,Assessing safety at the end of clinical trials using system organ classes: A case and comparative study.,"Carragher R, Robertson C.",,Pharmaceutical statistics,2021,2021-06-24,N,Safety; False Discovery Rate; Adverse Events; System Organ Class; Bayesian Hierarchy,,,"Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low-incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.",,doi:https://doi.org/10.1002/pst.2148 35921096,https://doi.org/10.1001/jamacardio.2022.2333,Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.,"Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",,JAMA cardiology,2022,2022-09-01,N,,,,"

Importance

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.

Objective

To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.

Design, setting, and participants

Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.

Exposures

Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.

Main outcomes and measures

Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.

Results

Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).

Conclusions and relevance

Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",,doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333 -34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083 34399584,https://doi.org/10.1161/strokeaha.120.032619,Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.,"Abraham G, Rutten-Jacobs L, Inouye M.",,Stroke,2021,2021-08-17,N,Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment,,,"Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",,doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619 +34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083 34890511,https://doi.org/10.1080/09638288.2021.1992517,"""It's been a long hard road"": challenges faced in the first three years following traumatic brain injury.","Downing MG, Hicks AJ, Braaf S, Myles DB, Gabbe BJ, Ponsford J.",,Disability and rehabilitation,2022,2021-12-10,N,Recovery; Challenges; Traumatic brain injury; Outcome; Qualitative Study,,,"

Purpose

There is limited qualitative research exploring challenges experienced following severe traumatic brain injury (TBI). We investigated challenges to recovery identified by individuals who sustained severe TBI three years earlier or their close others (COs), as well as suggestions for managing these challenges.

Materials and methods

Nine participants with TBI and 16 COs completed semi-structured interviews. Using reflexive thematic analysis, challenges were identified across several timeframes (i.e., at the injury, acute care, inpatient rehabilitation, outpatient rehabilitation, and at home/other location).

Results

Challenges experienced across all timeframes included: lack of information and poor communication, pre-existing conditions, missed injuries, and issues with medical staff, and continuity of care. From acute care onwards, there were TBI-related consequences, issues with coping and emotional adjustment, negative outlook, insufficient treatment, lack of support for COs, and issues with compensation and funding for rehabilitation needs. Some challenges were unique to a specific timeframe (e.g., over-stimulating ward setting during acute care, and limited or unsupportive families once injured individuals went home). Suggestions for managing some of the challenges were provided (e.g., information provision, having peer supports).

Conclusion

Suggestions should be considered to promote successful outcomes following severe TBI.IMPLICATIONS FOR REHABILITATIONRecovery following a severe traumatic brain injury can be hindered by challenges, such as poor communication, limited information provision, injury-related consequences, limited services and emotional support for the injured individual and their Close Others, and a need for education of the broader community about traumatic brain injury.Suggestions for managing these challenges (e.g., peer supports; services closer to home) could be used to inform clinical guidelines that could be used in a rehabilitation context.These suggestions ultimately aim to improve the post-injury experience and outcomes of individuals with traumatic brain injury and their Close Others.",,doi:https://doi.org/10.1080/09638288.2021.1992517 36581539,https://doi.org/10.1016/j.jpsychires.2022.12.015,"Corrigendum ""Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting"" [J. Psychiatr. Res. 153 (2022) 167-173].","Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2023,2022-12-28,N,,,,,,doi:https://doi.org/10.1016/j.jpsychires.2022.12.015 37516479,https://doi.org/10.1016/s2468-2667(23)00126-3,"Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.","Kennedy N, Win TL, Bandyopadhyay A, Kennedy J, Rowe B, McNerney C, Evans J, Hughes K, Bellis MA, Jones A, Harrington K, Moore S, Brophy S.",,The Lancet. Public health,2023,2023-08-01,N,,,,"

Background

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.

Methods

This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome.

Findings

After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident.

Interpretation

The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals.

Funding

National Institute for Health Research.",,doi:https://doi.org/10.1016/S2468-2667(23)00126-3 36013179,https://doi.org/10.3390/jpm12081230,Grip Strength Trajectories and Cognition in English and Chilean Older Adults: A Cross-Cohort Study.,"Angel B, Ajnakina O, Albala C, Lera L, Márquez C, Leipold L, Bilovich A, Dobson R, Bendayan R.",,Journal of personalized medicine,2022,2022-07-27,Y,Cognition; Longitudinal study; Older Adults; Grip Strength,,,"Growing evidence about the link between cognitive and physical decline suggests the early changes in physical functioning as a potential biomarker for cognitive impairment. Thus, we compared grip-strength trajectories over 12-16 years in three groups classified according to their cognitive status (two stable patterns, normal and impaired cognitive performance, and a declining pattern) in two representative UK and Chilean older adult samples. The samples consisted of 7069 UK (ELSA) and 1363 Chilean participants (ALEXANDROS). Linear Mixed models were performed. Adjustments included socio-demographics and health variables. The Declined and Impaired group had significantly lower grip-strength at baseline when compared to the Non-Impaired. In ELSA, the Declined and Impaired showed a faster decline in their grip strength compared to the Non-Impaired group but differences disappeared in the fully adjusted models. In ALEXANDROS, the differences were only found between the Declined and Non-Impaired and they were partially attenuated by covariates. Our study provides robust evidence of the association between grip strength and cognitive performance and how socio-economic factors might be key to understanding this association and their variability across countries. This has implications for future epidemiological research, as hand-grip strength measurements have the potential to be used as an indicator of cognitive performance.",,doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render -37067859,https://doi.org/10.1136/bmjmed-2022-000245,Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.,"Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",,BMJ medicine,2023,2023-02-14,Y,epidemiology; Heart Failure; Cardiology; Covid-19,,,"

Objective

To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.

Design

Registry based observational study.

Setting

74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.

Participants

All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).

Main outcome measures

Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.

Results

Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).

Conclusions

In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",,doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render 31153319,https://doi.org/10.1121/1.5100272,Developing a large scale population screening tool for the assessment of Parkinson's disease using telephone-quality voice.,"Arora S, Baghai-Ravary L, Tsanas A.",,The Journal of the Acoustical Society of America,2019,2019-05-01,N,,Applied Analytics,neurological,"Recent studies have demonstrated that analysis of laboratory-quality voice recordings can be used to accurately differentiate people diagnosed with Parkinson's disease (PD) from healthy controls (HCs). These findings could help facilitate the development of remote screening and monitoring tools for PD. In this study, 2759 telephone-quality voice recordings from 1483 PD and 15 321 recordings from 8300 HC participants were analyzed. To account for variations in phonetic backgrounds, data were acquired from seven countries. A statistical framework for analyzing voice was developed, whereby 307 dysphonia measures that quantify different properties of voice impairment, such as breathiness, roughness, monopitch, hoarse voice quality, and exaggerated vocal tremor, were computed. Feature selection algorithms were used to identify robust parsimonious feature subsets, which were used in combination with a random forests (RFs) classifier to accurately distinguish PD from HC. The best tenfold cross-validation performance was obtained using Gram-Schmidt orthogonalization and RF, leading to mean sensitivity of 64.90% (standard deviation, SD, 2.90%) and mean specificity of 67.96% (SD 2.90%). This large scale study is a step forward toward assessing the development of a reliable, cost-effective, and practical clinical decision support tool for screening the population at large for PD using telephone-quality voice.",,doi:https://doi.org/10.1121/1.5100272; html:https://europepmc.org/articles/PMC6509044; pdf:https://europepmc.org/articles/PMC6509044?pdf=render; doi:https://doi.org/10.1121/1.5100272 +37067859,https://doi.org/10.1136/bmjmed-2022-000245,Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.,"Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",,BMJ medicine,2023,2023-02-14,Y,epidemiology; Heart Failure; Cardiology; Covid-19,,,"

Objective

To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.

Design

Registry based observational study.

Setting

74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.

Participants

All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).

Main outcome measures

Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.

Results

Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).

Conclusions

In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",,doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render 33653161,https://doi.org/10.1177/1740774520976617,Making a distinction between data cleaning and central monitoring in clinical trials.,"Love SB, Yorke-Edwards V, Diaz-Montana C, Murray ML, Masters L, Gabriel M, Joffe N, Sydes MR.",,"Clinical trials (London, England)",2021,2021-03-02,Y,,,,,,doi:https://doi.org/10.1177/1740774520976617; html:https://europepmc.org/articles/PMC8174009; pdf:https://europepmc.org/articles/PMC8174009?pdf=render 36707908,https://doi.org/10.1186/s13643-023-02173-w,A comparison of international modelling methods to evaluate health economics of colorectal cancer screening: a systematic review protocol.,"Adair O, McFerran E, Owen T, McKee C, Lamrock F, Lawler M.",,Systematic reviews,2023,2023-01-27,Y,Screening; Economic evaluation; Colorectal Cancer; Health Economics; Cost-effectiveness Analysis; Quality-adjusted Life Years; Cost-utility; Incremental Cost-effectiveness Ratio; Cost–benefit; Life Years Gained,,,"

Background

Colorectal cancer (CRC) is becoming an increasing health problem worldwide. However, with the help of screening, early diagnosis can reduce incidence and mortality rates. To elevate the economic burden that CRC can cause, cost-effectiveness analysis (CEA) can assist healthcare systems to make screening programmes more cost-effective and prolong survival for early-stage CRC patients. This review aims to identify different CEA modelling methods used internationally to evaluate health economics of CRC screening.

Methods

This review will systematically search electronic databases which include MEDLINE, EMBASE, Web of Science and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance recommendations will design the review, and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement will be used to extract relevant data from studies retrieved. Two reviewers will screen through the evidence using the PICOS (Participant, Intervention, Comparators, Outcomes, Study Design) framework, with a third reviewer to settle any disagreements. Once data extraction and quality assessment are complete, the results will be presented qualitatively and tabulated using the CHEERS checklist.

Discussion

The results obtained from the systematic review will highlight how different CRC screening programmes around the world utilise and incorporate health economic modelling methods to be more cost-effective. This information can help modellers develop CEA models which can be adapted to suit the specific screening programmes that they are evaluating.

Systematic review registration

PROSPERO CRD42022296113.",,doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?pdf=render PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality on respiratory health in children,"Holden K, Lee A, Hawcutt D, Sinha I.",,"Breathe (Sheffield, England)",2023,2023-06-01,Y,,,,"It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.

Educational aims

The reader should understand how housing quality and indoor air quality affect respiratory health in children. The reader should understand which children are at most risk of living in poor-quality housing. The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people. Tweetable abstract Poor-quality housing negatively impacts the quality of the air that children breathe in their living environment, which is detrimental to their respiratory health. Urgent action is needed to improve housing quality to improve child respiratory health. https://bit.ly/3pshb34",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461733/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461733/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render @@ -857,17 +860,17 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 36825398,https://doi.org/10.1097/mcp.0000000000000948,Effectiveness and safety of coronavirus disease 2019 vaccines.,"Shi T, Robertson C, Sheikh A.",,Current opinion in pulmonary medicine,2023,2023-02-24,Y,,,,"

Purpose of review

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

Recent findings

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

Summary

The findings from this paper support current recommendations that vaccination remains the safest way for adults, pregnant women, children and adolescents to be protected against COVID-19. There is a need to continue to monitor the effectiveness and safety of COVID-19 vaccines as these continue to be deployed in the evolving pandemic.",,doi:https://doi.org/10.1097/MCP.0000000000000948; html:https://europepmc.org/articles/PMC10090353; pdf:https://europepmc.org/articles/PMC10090353?pdf=render 34516619,https://doi.org/10.1093/ehjci/jeab178,Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.,"Taha K, Verstraelen TE, de Brouwer R, de Bruin-Bon RHACM, Cramer MJ, Te Rijdt WP, Bouma BJ, de Boer RA, Doevendans PA, Asselbergs FW, Wilde AAM, van den Berg MP, Teske AJ.",,European heart journal. Cardiovascular Imaging,2022,2022-10-01,Y,Risk stratification; ventricular arrhythmia; Phospholamban; Mechanical Dispersion; Deformation Imaging; Genetic Cardiomyopathy,,,"

Aims

Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.

Methods and results

We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD >45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF <45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)].

Conclusion

LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.",,doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render 35135774,https://doi.org/10.1136/bmjopen-2021-055603,"Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.","Clarke CS, Williamson E, Denaxas S, Carpenter JR, Thomas M, Blackshaw H, Schilder AGM, Philpott CM, Hopkins C, Morris S, MACRO programme team.",,BMJ open,2022,2022-02-08,Y,Otolaryngology; Clinical Trials; Health Economics,,,"

Objectives

Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England.

Design

Observational retrospective study examining cost of healthcare of patients receiving CRS surgery.

Setting

Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England.

Participants

A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps.

Outcome measures

Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources.

Results

Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery.

Conclusions

We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.",,doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render -37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render 34985035,https://doi.org/10.1097/htr.0000000000000741,Epidemiology and 6- and 12-Month Outcomes of Intimate Partner Violence and Other Violence-Related Traumatic Brain Injury in Major Trauma: A Population-Based Trauma Registry Study.,"Gabbe BJ, Braaf S, Cameron PA, Berecki-Gisolf J.",,The Journal of head trauma rehabilitation,2022,2022-01-01,N,,,,"

Objective

To compare the epidemiology, in-hospital outcomes, and 6-month and 12-month patient-reported, outcomes of major trauma patients with intimate partner violence (IPV)-related traumatic brain injury (TBI) with other interpersonal violence (OV)-related TBI.

Setting

Victoria, Australia.

Participants

Adult (≥18 years) major trauma cases with TBI (concussion, skull fracture, or intracranial injury), injured through IPV or OV, between July 2010 and June 2020, and included on the population-based Victorian State Trauma Registry. There were 133 adult major trauma cases due to IPV and 1796 due to OV. The prevalence of TBI was 39% (n = 52) in the IPV group and 56% (n = 1010) in the OV group.

Design

Registry-based cohort study.

Main measures

Trauma care indicators and 6- and 12-month patient-reported outcomes (self-reported disability, Glasgow Outcome Scale-Extended, EQ-5D-3L, and return to work).

Results

The annual incidence (95% CI) of major trauma involving TBI was 0.11 (0.08-0.14) per 100 000 population for IPV and 2.11 (1.98-2.24) per 100 000 for OV. A higher proportion of IPV-related cases were women (73% vs 5%), had sustained a severe TBI (Glasgow Coma Scale score 3-8; 27% vs 15%), were admitted to intensive care (56% vs 37%), and died in hospital (14% vs 5%). The median (interquartile range) time to definitive care (4.7 hours vs 3.3 hours) and head computed tomographic scan (5.0 hours vs 3.1 hours) was longer in the IPV group. Follow-up rates at 6 and 12 months were 71% and 69%, respectively. The 6- and 12-month outcomes were generally poorer in the IPV-related group.

Conclusion

The incidence of IPV-related major trauma with TBI was low. However, the prevalence of severe TBI, the time to key aspects of clinical care, in-hospital mortality, and longer-term work-related disability were higher. However, power to detect differences was low due to the small number of IPV-related cases compared with the OV group.",,doi:https://doi.org/10.1097/HTR.0000000000000741 -32954362,https://doi.org/10.1038/s43016-020-0093-y,Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2020,2020-06-22,N,,,,"Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.",,doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y +37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render 34847088,https://doi.org/10.1097/ede.0000000000001429,The Authors Respond.,"Katsoulis M, De Stavola B, Lai AG, Gomes M, Diaz-Ordaz K.",,"Epidemiology (Cambridge, Mass.)",2022,2022-01-01,N,,,,,,doi:https://doi.org/10.1097/EDE.0000000000001429 31416346,https://doi.org/10.1161/circulationaha.119.041980,Machine Learning to Predict the Likelihood of Acute Myocardial Infarction.,"Than MP, Pickering JW, Sandoval Y, Shah ASV, Tsanas A, Apple FS, Blankenberg S, Cullen L, Mueller C, Neumann JT, Twerenbold R, Westermann D, Beshiri A, Mills NL, MI3 Collaborative.",,Circulation,2019,2019-08-16,Y,Troponin; Myocardial infarction; acute coronary syndrome; Machine Learning,Applied Analytics,,"

Background

Variations in cardiac troponin concentrations by age, sex, and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients.

Methods

A machine learning algorithm (myocardial-ischemic-injury-index [MI3]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3013 patients and tested on 7998 patients with suspected myocardial infarction. MI3 uses gradient boosting to compute a value (0-100) reflecting an individual's likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value, specificity and positive predictive value for that individual. Assessment was by calibration and area under the receiver operating characteristic curve. Secondary analysis evaluated example MI3 thresholds from the training set that identified patients as low risk (99% sensitivity) and high risk (75% positive predictive value), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology rule-out pathways.

Results

Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI3 was well calibrated with a very high area under the receiver operating characteristic curve of 0.963 [0.956-0.971] in the test set and similar performance in early and late presenters. Example MI3 thresholds identifying low- and high-risk patients in the training set were 1.6 and 49.7, respectively. In the test set, MI3 values were <1.6 in 69.5% with a negative predictive value of 99.7% (99.5-99.8%) and sensitivity of 97.8% (96.7-98.7%), and were ≥49.7 in 10.6% with a positive predictive value of 71.8% (68.9-75.0%) and specificity of 96.7% (96.3-97.1%). Using these thresholds, MI3 performed better than the European Society of Cardiology 0/3-hour pathway (sensitivity, 82.5% [74.5-88.8%]; specificity, 92.2% [90.7-93.5%]) and the 99th percentile at any time point (sensitivity, 89.6% [87.4-91.6%]); specificity, 89.3% [88.6-90.0%]).

Conclusions

Using machine learning, MI3 provides an individualized and objective assessment of the likelihood of myocardial infarction, which can be used to identify low- and high-risk patients who may benefit from earlier clinical decisions.

Clinical trial registration

URL: https://www.anzctr.org.au. Unique identifier: ACTRN12616001441404.",,doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041980; html:https://europepmc.org/articles/PMC6749969; pdf:https://europepmc.org/articles/PMC6749969?pdf=render; doi:https://doi.org/10.1161/circulationaha.119.041980 +32954362,https://doi.org/10.1038/s43016-020-0093-y,Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2020,2020-06-22,N,,,,"Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.",,doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y 37074763,https://doi.org/10.2196/44237,Data-Driven Identification of Unusual Prescribing Behavior: Analysis and Use of an Interactive Data Tool Using 6 Months of Primary Care Data From 6500 Practices in England.,"Hopcroft LE, Massey J, Curtis HJ, Mackenna B, Croker R, Brown AD, O'Dwyer T, Macdonald O, Evans D, Inglesby P, Bacon SC, Goldacre B, Walker AJ.",,JMIR medical informatics,2023,2023-04-19,Y,General Practice; Prescribing; Primary Care; Electronic Health Records; Ehr; Outliers; Dashboard; Data Science,,,"

Background

Approaches to addressing unwarranted variation in health care service delivery have traditionally relied on the prospective identification of activities and outcomes, based on a hypothesis, with subsequent reporting against defined measures. Practice-level prescribing data in England are made publicly available by the National Health Service (NHS) Business Services Authority for all general practices. There is an opportunity to adopt a more data-driven approach to capture variability and identify outliers by applying hypothesis-free, data-driven algorithms to national data sets.

Objective

This study aimed to develop and apply a hypothesis-free algorithm to identify unusual prescribing behavior in primary care data at multiple administrative levels in the NHS in England and to visualize these results using organization-specific interactive dashboards, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to quantify how ""unusual"" the prescribing rates of a particular chemical within an organization are as compared to peer organizations, over a period of 6 months (June-December 2021). This is followed by a ranking to identify which chemicals are the most notable outliers in each organization. These outlying chemicals are calculated for all practices, primary care networks, clinical commissioning groups, and sustainability and transformation partnerships in England. Our results are presented via organization-specific interactive dashboards, the iterative development of which has been informed by user feedback.

Results

We developed interactive dashboards for every practice (n=6476) in England, highlighting the unusual prescribing of 2369 chemicals (dashboards are also provided for 42 sustainability and transformation partnerships, 106 clinical commissioning groups, and 1257 primary care networks). User feedback and internal review of case studies demonstrate that our methodology identifies prescribing behavior that sometimes warrants further investigation or is a known issue.

Conclusions

Data-driven approaches have the potential to overcome existing biases with regard to the planning and execution of audits, interventions, and policy making within NHS organizations, potentially revealing new targets for improved health care service delivery. We present our dashboards as a proof of concept for generating candidate lists to aid expert users in their interpretation of prescribing data and prioritize further investigations and qualitative research in terms of potential targets for improved performance.",,doi:https://doi.org/10.2196/44237; html:https://europepmc.org/articles/PMC10162592 32665523,https://doi.org/10.1097/hjh.0000000000002579,Association of SBP and BMI with cognitive and structural brain phenotypes in UK Biobank.,"Ferguson AC, Tank R, Lyall LM, Ward J, Welsh P, Celis-Morales C, McQueenie R, Strawbridge RJ, Mackay DF, Pell JP, Smith DJ, Sattar N, Cavanagh J, Lyall DM.",,Journal of hypertension,2020,2020-12-01,N,,,,"

Objective

To test for associations between SBP and BMI, with domain-specific cognitive abilities and examine which brain structural phenotypes mediate those associations.

Methods

Using cross-sectional UK Biobank data (final N = 28 412), we examined SBP/BMI vs. cognitive test scores of pairs-matching, matrix completion, trail making test A/B, digit symbol substitution, verbal-numerical reasoning, tower rearranging and simple reaction time. We adjusted for potential confounders of age, sex, deprivation, medication, apolipoprotein e4 genotype, smoking, population stratification and genotypic array. We tested for mediation via multiple structural brain imaging phenotypes and corrected for multiple testing with false discovery rate.

Results

We found positive associations for higher BMI with worse reaction time, reasoning, tower rearranging and matrix completion tasks by 0.024-0.067 SDs per BMI SD (all P < 0.001). Higher SBP was associated with worse reasoning (0.034 SDs) and matrix completion scores (-0.024 SDs; both P < 0.001). Both BMI and SBP were associated with multiple brain structural metrics including total grey/white matter volumes, frontal lobe volumes, white matter tract integrity and white matter hyperintensity volumes: specific metrics mediated around one-third of the associations with cognition.

Conclusion

Our findings add to the body of evidence that addressing cardiovascular risk factors may also preserve cognitive function, via specific aspects of brain structure.",,doi:https://doi.org/10.1097/HJH.0000000000002579 34026049,https://doi.org/10.12688/f1000research.25484.2,PUblications Metadata Augmentation (PUMA) pipeline.,"Butters OW, Wilson RC, Garner H, Burton TWY.",,F1000Research,2020,2020-09-04,Y,bibliometrics; Bibliography; Alspac; Longitudinal Birth Cohort,,,"Cohort studies collect, generate and distribute data over long periods of time - often over the lifecourse of their participants. It is common for these studies to host a list of publications (which can number many thousands) on their website to demonstrate the impact of the study and facilitate the search of existing research to which the study data has contributed. The ability to search and explore these publication lists varies greatly between studies. We believe a lack of rich search and exploration functionality of study publications is a barrier to entry for new or prospective users of a study's data, since it may be difficult to find and evaluate previous work in a given area. These lists of publications are also typically manually curated, resulting in a lack of rich metadata to analyse, making bibliometric analysis difficult. We present here a software pipeline that aggregates metadata from a variety of third-party providers to power a web based search and exploration tool for lists of publications. Alongside core publication metadata (i.e. author lists, keywords etc.), we include geocoding of first authors and citation counts in our pipeline. This allows a characterisation of a study as a whole based on common locations of authors, frequency of keywords, citation profile etc. This enriched publications metadata can be useful for generating study impact metrics and web-based graphics for public dissemination. In addition, the pipeline produces a research data set for bibliometric analysis or social studies of science. We use a previously published list of publications from a cohort study as an exemplar input data set to show the output and utility of the pipeline here.",,doi:https://doi.org/10.12688/f1000research.25484.2; html:https://europepmc.org/articles/PMC8108552; pdf:https://europepmc.org/articles/PMC8108552?pdf=render 36501061,https://doi.org/10.3390/nu14235031,Associations of Genetically Predicted Vitamin B12 Status across the Phenome.,"Dib MJ, Ahmadi KR, Zagkos L, Gill D, Morris B, Elliott P, Dehghan A, Tzoulaki I.",,Nutrients,2022,2022-11-26,Y,Vitamin B12; Deficiency; epidemiology; Mendelian Randomisation; Pernicious Anaemia,,,"Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.",,doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render -37119604,https://doi.org/10.1016/j.canep.2023.102367,"Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.","Greene GJ, Thomson CS, Donnelly D, Chung D, Bhatti L, Gavin AT, Lawler M, Huws DW, Rolles MJ, Bennée F, Morrison DS.",,Cancer epidemiology,2023,2023-04-21,Y,Pandemic; Population-based Incidence; Covid-19; Sars-cov-2; Pathology-Confirmed Cancer,,,"

Introduction

The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI).

Methods

Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR).

Results

Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20).

Conclusion

PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.",,doi:https://doi.org/10.1016/j.canep.2023.102367; html:https://europepmc.org/articles/PMC10121133; pdf:https://europepmc.org/articles/PMC10121133?pdf=render 34671274,https://doi.org/10.3389/fphys.2021.730736,Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.,"Roudijk RW, Boonstra MJ, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, van Dam PM, Loh P.",,Frontiers in physiology,2021,2021-10-04,Y,Cardiac Arrhythmia; Sudden Cardiac Death; Electroanatomical Mapping; Electrocardiographic Imaging (Ecgi); Non-invasive Mapping; Equivalent Dipole Layer; Inverse Problem Of Electrocardiography,,,"This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49-0.59] for epicardial activation, 0.50 ± 0.27 [0.41-0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32-0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9-29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.",,doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render +37119604,https://doi.org/10.1016/j.canep.2023.102367,"Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.","Greene GJ, Thomson CS, Donnelly D, Chung D, Bhatti L, Gavin AT, Lawler M, Huws DW, Rolles MJ, Bennée F, Morrison DS.",,Cancer epidemiology,2023,2023-04-21,Y,Pandemic; Population-based Incidence; Covid-19; Sars-cov-2; Pathology-Confirmed Cancer,,,"

Introduction

The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI).

Methods

Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR).

Results

Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20).

Conclusion

PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.",,doi:https://doi.org/10.1016/j.canep.2023.102367; html:https://europepmc.org/articles/PMC10121133; pdf:https://europepmc.org/articles/PMC10121133?pdf=render 36942567,https://doi.org/10.1161/circep.122.011585,Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.,"Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",,Circulation. Arrhythmia and electrophysiology,2023,2023-03-21,N,Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity,,,"

Background

A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.

Methods

We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA2DS2-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA2DS2-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA2DS2-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.

Results

In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; P=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; P=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; P=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; P=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- P=0.027) but not in OptumLabs (interaction-P=0.720). ERC was not associated with an increased risk for the primary safety outcome.

Conclusions

ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA2DS2-VASc score ≥4).",,doi:https://doi.org/10.1161/CIRCEP.122.011585 33468531,https://doi.org/10.1136/bmjopen-2020-047101,Protocol for the development of the Wales Multimorbidity e-Cohort (WMC): data sources and methods to construct a population-based research platform to investigate multimorbidity.,"Lyons J, Akbari A, Agrawal U, Harper G, Azcoaga-Lorenzo A, Bailey R, Rafferty J, Watkins A, Fry R, McCowan C, Dezateux C, Robson JP, Peek N, Holmes C, Denaxas S, Owen R, Abrams KR, John A, O'Reilly D, Richardson S, Hall M, Gale CP, Davies J, Davies C, Cross L, Gallacher J, Chess J, Brookes AJ, Lyons RA.",,BMJ open,2021,2021-01-19,Y,epidemiology; Public Health; Primary Care; Geriatric Medicine; Health Policy,,,"

Introduction

Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence.We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity.

Methods and analysis

The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity.Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation.

Ethics and dissemination

The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?pdf=render 32908801,https://doi.org/10.1167/tvst.9.9.38,Merging Information From Infrared and Autofluorescence Fundus Images for Monitoring of Chorioretinal Atrophic Lesions.,"Ometto G, Montesano G, Sadeghi Afgeh S, Lazaridis G, Liu X, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2020,2020-08-25,Y,Autofluorescence; Segmentation; infrared; Uveitis; Multimodal,,,"

Purpose

To develop a method for automated detection and progression analysis of chorioretinal atrophic lesions using the combined information of standard infrared (IR) and autofluorescence (AF) fundus images.

Methods

Eighteen eyes (from 16 subjects) with punctate inner choroidopathy were analyzed. Macular IR and blue AF images were acquired in all eyes with a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Two clinical experts manually segmented chorioretinal lesions on the AF image. AF images were aligned to the corresponding IR. Two random forest models were trained to classify pixels of lesions, one based on the AF image only, the other based on the aligned IR-AF. The models were validated using a leave-one-out cross-validation and were tested against the manual segmentation to compare their performance. A time series from one eye was identified and used to evaluate the method based on the IR-AF in a case study.

Results

The method based on the AF images correctly classified 95% of the pixels (i.e., in vs. out of the lesion) with a Dice's coefficient of 0.80. The method based on the combined IR-AF correctly classified 96% of the pixels with a Dice's coefficient of 0.84.

Conclusions

The automated segmentation of chorioretinal lesions using IR and AF shows closer alignment to manual segmentation than the same method based on AF only. Merging information from multimodal images improves the automatic and objective segmentation of chorioretinal lesions even when based on a small dataset.

Translational relevance

Merged information from multimodal images improves segmentation performance of chorioretinal lesions.",,doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?pdf=render @@ -878,20 +881,20 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 34328624,https://doi.org/10.1007/s11695-021-05493-9,30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.,"Singhal R, Ludwig C, Rudge G, Gkoutos GV, Tahrani A, Mahawar K, GENEVA Collaborators, Pędziwiatr M, Major P, Zarzycki P, Pantelis A, Lapatsanis DP, Stravodimos G, Matthys C, Focquet M, Vleeschouwers W, Spaventa AG, Zerrweck C, Vitiello A, Berardi G, Musella M, Sanchez-Meza A, Cantu FJ, Mora F, Cantu MA, Katakwar A, Reddy DN, Elmaleh H, Hassan M, Elghandour A, Elbanna M, Osman A, Khan A, Layani L, Kiran N, Velikorechin A, Solovyeva M, Melali H, Shahabi S, Agrawal A, Shrivastava A, Sharma A, Narwaria B, Narwaria M, Raziel A, Sakran N, Susmallian S, Karagöz L, Akbaba M, Pişkin SZ, Balta AZ, Senol Z, Manno E, Iovino MG, Osman A, Qassem M, Arana-Garza S, Povoas HP, Vilas-Boas ML, Naumann D, Super J, Li A, Ammori BJ, Balamoun H, Salman M, Nasta AM, Goel R, Sánchez-Aguilar H, Herrera MF, Abou-Mrad A, Cloix L, Mazzini GS, Kristem L, Lazaro A, Campos J, Bernardo J, González J, Trindade C, Viveiros O, Ribeiro R, Goitein D, Hazzan D, Segev L, Beck T, Reyes H, Monterrubio J, García P, Benois M, Kassir R, Contine A, Elshafei M, Aktas S, Weiner S, Heidsieck T, Level L, Pinango S, Ortega PM, Moncada R, Valenti V, Vlahović I, Boras Z, Liagre A, Martini F, Juglard G, Motwani M, Saggu SS, Al Moman H, López LAA, Cortez MAC, Zavala RA, D'Haese C, Kempeneers I, Himpens J, Lazzati A, Paolino L, Bathaei S, Bedirli A, Yavuz A, Büyükkasap Ç, Özaydın S, Kwiatkowski A, Bartosiak K, Walędziak M, Santonicola A, Angrisani L, Iovino P, Palma R, Iossa A, Boru CE, De Angelis F, Silecchia G, Hussain A, Balchandra S, Coltell IB, Pérez JL, Bohra A, Awan AK, Madhok B, Leeder PC, Awad S, Al-Khyatt W, Shoma A, Elghadban H, Ghareeb S, Mathews B, Kurian M, Larentzakis A, Vrakopoulou GZ, Albanopoulos K, Bozdag A, Lale A, Kirkil C, Dincer M, Bashir A, Haddad A, Hijleh LA, Zilberstein B, de Marchi DD, Souza WP, Brodén CM, Gislason H, Shah K, Ambrosi A, Pavone G, Tartaglia N, Kona SLK, Kalyan K, Perez CEG, Botero MAF, Covic A, Timofte D, Maxim M, Faraj D, Tseng L, Liem R, Ören G, Dilektasli E, Yalcin I, AlMukhtar H, Al Hadad M, Mohan R, Arora N, Bedi D, Rives-Lange C, Chevallier JM, Poghosyan T, Sebbag H, Zinaï L, Khaldi S, Mauchien C, Mazza D, Dinescu G, Rea B, Pérez-Galaz F, Zavala L, Besa A, Curell A, Balibrea JM, Vaz C, Galindo L, Silva N, Caballero JLE, Sebastian SO, Marchesini JCD, da Fonseca Pereira RA, Sobottka WH, Fiolo FE, Turchi M, Coelho ACJ, Zacaron AL, Barbosa A, Quinino R, Menaldi G, Paleari N, Martinez-Duartez P, de Aragon Ramírez de Esparza GM, Esteban VS, Torres A, Garcia-Galocha JL, Josa M, Pacheco-Garcia JM, Mayo-Ossorio MA, Chowbey P, Soni V, de Vasconcelos Cunha HA, Castilho MV, Ferreira RMA, Barreiro TA, Charalabopoulos A, Sdralis E, Davakis S, Bomans B, Dapri G, Van Belle K, Takieddine M, Vaneukem P, Karaca ESA, Karaca FC, Sumer A, Peksen C, Savas OA, Chousleb E, Elmokayed F, Fakhereldin I, Aboshanab HM, Swelium T, Gudal A, Gamloo L, Ugale A, Ugale S, Boeker C, Reetz C, Hakami IA, Mall J, Alexandrou A, Baili E, Bodnar Z, Maleckas A, Gudaityte R, Guldogan CE, Gundogdu E, Ozmen MM, Thakkar D, Dukkipati N, Shah PS, Shah SS, Shah SS, Adil MT, Jambulingam P, Mamidanna R, Whitelaw D, Adil MT, Jain V, Veetil DK, Wadhawan R, Torres A, Torres M, Tinoco T, Leclercq W, Romeijn M, van de Pas K, Alkhazraji AK, Taha SA, Ustun M, Yigit T, Inam A, Burhanulhaq M, Pazouki A, Eghbali F, Kermansaravi M, Jazi AHD, Mahmoudieh M, Mogharehabed N, Tsiotos G, Stamou K, Barrera Rodriguez FJ, Rojas Navarro MA, Torres OM, Martinez SL, Tamez ERM, Millan Cornejo GA, Flores JEG, Mohammed DA, Elfawal MH, Shabbir A, Guowei K, So JB, Kaplan ET, Kaplan M, Kaplan T, Pham D, Rana G, Kappus M, Gadani R, Kahitan M, Pokharel K, Osborne A, Pournaras D, Hewes J, Napolitano E, Chiappetta S, Bottino V, Dorado E, Schoettler A, Gaertner D, Fedtke K, Aguilar-Espinosa F, Aceves-Lozano S, Balani A, Nagliati C, Pennisi D, Rizzi A, Frattini F, Foschi D, Benuzzi L, Parikh C, Shah H, Pinotti E, Montuori M, Borrelli V, Dargent J, Copaescu CA, Hutopila I, Smeu B, Witteman B, Hazebroek E, Deden L, Heusschen L, Okkema S, Aufenacker T, den Hengst W, Vening W, van der Burgh Y, Ghazal A, Ibrahim H, Niazi M, Alkhaffaf B, Altarawni M, Cesana GC, Anselmino M, Uccelli M, Olmi S, Stier C, Akmanlar T, Sonnenberg T, Schieferbein U, Marcolini A, Awruch D, Vicentin M, de Souza Bastos EL, Gregorio SA, Ahuja A, Mittal T, Bolckmans R, Wiggins T, Baratte C, Wisnewsky JA, Genser L, Chong L, Taylor L, Ward S, Chong L, Taylor L, Hi MW, Heneghan H, Fearon N, Plamper A, Rheinwalt K, Heneghan H, Geoghegan J, Ng KC, Fearon N, Kaseja K, Kotowski M, Samarkandy TA, Leyva-Alvizo A, Corzo-Culebro L, Wang C, Yang W, Dong Z, Riera M, Jain R, Hamed H, Said M, Zarzar K, Garcia M, Türkçapar AG, Şen O, Baldini E, Conti L, Wietzycoski C, Lopes E, Pintar T, Salobir J, Aydin C, Atici SD, Ergin A, Ciyiltepe H, Bozkurt MA, Kizilkaya MC, Onalan NBD, Zuber MNBA, Wong WJ, Garcia A, Vidal L, Beisani M, Pasquier J, Vilallonga R, Sharma S, Parmar C, Lee L, Sufi P, Sinan H, Saydam M.",,Obesity surgery,2021,2021-07-30,Y,Pandemic; Obesity Surgery; Bariatric Surgery; Revisional Surgery; Covid-19; Sars-cov-2,,,"

Background

There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates.

Methods

We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020.

Results

Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country.

Conclusions

BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak.",,doi:https://doi.org/10.1007/s11695-021-05493-9; html:https://europepmc.org/articles/PMC8323543; pdf:https://europepmc.org/articles/PMC8323543?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s11695-021-05493-9.pdf 32946551,https://doi.org/10.1093/ageing/afaa158,Do home modifications reduce care home admissions for older people? A matched control evaluation of the Care & Repair Cymru service in Wales.,"Hollinghurst J, Fry R, Akbari A, Watkins A, Williams N, Hillcoat-Nallétamby S, Lyons RA, Clegg A, Rodgers SE.",,Age and ageing,2020,2020-10-01,Y,Frailty; Interventions; Older People; Care Homes; Administrative Data,,,"

Background

home advice and modification interventions aim to promote independent living for those living in the community, but quantitative evidence of their effectiveness is limited.

Aim

assess the risk of care home admissions for people with different frailty levels receiving home advice and modification interventions against a control group who do not.

Study design and setting

matched control evaluation using linked longitudinal data from the Secure Anonymised Information Linkage (SAIL) Databank, comprising people aged 60-95, registered with a SAIL contributing general practice. The intervention group received the Care & Repair Cymru (C & RC) service, a home advice and modification service available to residents in Wales.

Methods

frailty, age and gender were used in propensity score matching to assess the Hazard Ratio (HR) of care home admissions within a 1-, 3- and 5-year period for the intervention group (N = 93,863) compared to a matched control group (N = 93,863). Kaplan-Meier curves were used to investigate time to a care home admission.

Results

the intervention group had an increased risk of a care home admission at 1-, 3- and 5-years [HR (95%CI)] for those classified as fit [1-year: 2.02 (1.73, 2.36), 3-years: 1.87 (1.72, 2.04), 5-years: 1.99 (1.86, 2.13)] and mildly frail [1-year: 1.25 (1.09, 1.42), 3-years: 1.25 (1.17, 1.34), 5-years: 1.30 (1.23, 1.38)], but a reduced risk of care home admission for moderately [1-year: 0.66 (0.58, 0.75), 3-years: 0.75 (0.70, 0.80), 5-years: 0.83 (0.78, 0.88)] and severely frail individuals [1-year: 0.44 (0.37, 0.54), 3-years: 0.54 (0.49, 0.60), 5-years: 0.60(0.55, 0.66)].

Conclusions

HRs indicated that the C & RC service helped to prevent care home admissions for moderately and severely frail individuals. The HRs generally increased with follow-up duration.",,doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render 34088700,https://doi.org/10.2337/dc20-2518,"Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.","Mordi IR, Lumbers RT, Palmer CNA, Pearson ER, Sattar N, Holmes MV, Lang CC, HERMES Consortium.",,Diabetes care,2021,2021-06-04,Y,,,,"

Objective

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).

Research design and methods

Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators.

Results

Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11-1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00-1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01-2.19; P = 0.042), although again with evidence of pleiotropy.

Conclusions

These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.",,doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render; pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf -37394283,https://doi.org/10.1002/ehf2.14444,Survival after HeartMate 3 left ventricular assist device implantation: real-world data from Europe.,"Numan L, Schramm R, Oerlemans MIFJ, van der Kaaij NP, Aarts E, Ramjankhan FZ, Oppelaar AM, Morshuis M, Guenther SPW, Zimpfer D, Riebandt J, Wiedemann D, Asselbergs FW, Van Laake LW.",,ESC heart failure,2023,2023-07-02,Y,,,,,,doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444 32763878,https://doi.org/10.2196/18690,Notifications to Improve Engagement With an Alcohol Reduction App: Protocol for a Micro-Randomized Trial.,"Bell L, Garnett C, Qian T, Perski O, Potts HWW, Williamson E.",,JMIR research protocols,2020,2020-08-07,Y,Alcohol; Engagement; Mhealth; Mobile Health; Excessive Alcohol Consumption; Smartphone App; Push Notifications; Digital Behavior Change; Micro-randomized Trial,,,"

Background

Drink Less is a behavior change app that aims to help users in the general adult population reduce hazardous and harmful alcohol consumption. The app includes a daily push notification, delivered at 11 am, asking users to ""Please complete your mood and drinking diaries."" Previous analysis of Drink Less engagement data suggests the current notification strongly influences how users engage with the app in the subsequent hour. To exploit a potential increase of vulnerability of excess drinking and opportunity to engage with the app in the evenings, we changed the delivery time from 11 am to 8 pm. We now aim to further optimise the content and sequence of notifications, testing 30 new evidence-informed notifications targeting the user's perceived usefulness of the app.

Objective

The primary objective is to assess whether sending a notification at 8 pm increases behavioral engagement (opening the app) in the subsequent hour. Secondary objectives include comparing the effect of the new bank of messages with the standard message and effect moderation over time. We also aim to more generally understand the role notifications have on the overall duration, depth, and frequency of engagement with Drink Less over the first 30 days after download.

Methods

This is a protocol for a micro-randomized trial with two additional parallel arms. Inclusion criteria are Drink Less users who (1) consent to participate in the trial; (2) self-report a baseline Alcohol Use Disorders Identification Test score of 8 or above; (3) reside in the United Kingdom; (4) age ≥18 years and; (5) report interest in drinking less alcohol. In the micro-randomized trial, participants will be randomized daily at 8 pm to receive no notification, a notification with text from the new message bank, or the standard message. The primary outcome is the time-varying, binary outcome of ""Did the user open the app in the hour from 8 pm to 9 pm?"". The primary analysis will estimate the marginal relative risk for the notifications using an estimator developed for micro-randomized trials with binary outcomes. Participants randomized to the parallel arms will receive no notifications (Secondary Arm A), or the standard notification delivered daily at 11 am (Secondary Arm B) over 30 days, allowing the comparison of overall engagement between different notification delivery strategies.

Results

Approval was granted by the University College of London's Departmental Research Ethics Committee (CEHP/2016/556) on October 11, 2019, and The London School of Hygiene and Tropical Medicine Interventions Research Ethics Committee (17929) on November 27, 2019. Recruitment began on January 2, 2020, and is ongoing.

Conclusions

Understanding how push notifications may impact engagement with a behavior change app can lead to further improvements in engagement, and ultimately help users reduce their alcohol consumption. This understanding may also be generalizable to other apps that target a variety of behavior changes.

International registered report identifier (irrid)

DERR1-10.2196/18690.",,doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945 -37225263,https://doi.org/10.1136/bmjgast-2023-001139,Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them.,"Kyriacou M, Radford S, Moran GW, Focus group collaborators group.",,BMJ open gastroenterology,2023,2023-05-01,Y,Ulcerative colitis; Inflammatory Bowel Disease; Adjuvant Treatment,,,"

Background

Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management.

Methods

A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements.

Results

In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision.

Conclusions

We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.",,doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render +37394283,https://doi.org/10.1002/ehf2.14444,Survival after HeartMate 3 left ventricular assist device implantation: real-world data from Europe.,"Numan L, Schramm R, Oerlemans MIFJ, van der Kaaij NP, Aarts E, Ramjankhan FZ, Oppelaar AM, Morshuis M, Guenther SPW, Zimpfer D, Riebandt J, Wiedemann D, Asselbergs FW, Van Laake LW.",,ESC heart failure,2023,2023-07-02,Y,,,,,,doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444 36543768,https://doi.org/10.1038/s41467-022-35321-2,Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants.,"McCracken C, Raisi-Estabragh Z, Veldsman M, Raman B, Dennis A, Husain M, Nichols TE, Petersen SE, Neubauer S.",,Nature communications,2022,2022-12-21,Y,,,,"Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.",,doi:https://doi.org/10.1038/s41467-022-35321-2; html:https://europepmc.org/articles/PMC9772225; pdf:https://europepmc.org/articles/PMC9772225?pdf=render; pdf:https://www.nature.com/articles/s41467-022-35321-2.pdf -34427560,https://doi.org/10.1684/ejd.2021.4108,"The association between immunosuppression and skin cancer in solid organ transplant recipients: a control-matched cohort study of 2,852 patients.","Gibson JAG, Cordaro A, Dobbs TD, Griffiths R, Akbari A, Whitaker S, Hutchings HA, Lyons RA, Whitaker IS.",,European journal of dermatology : EJD,2021,2021-12-01,N,Transplant; Oncology; immunosuppression; Skin Cancer,,,"Skin cancer is more common in transplant recipients, although the quoted incidence is variable. This study investigated the incidence of skin cancer in solid organ transplant recipients (OTRs) in a national cohort and the effect of pharmacotherapeutic agents Transplant patients were identified from Patient Episode Database for Wales (PEDW) using Office of Population Census and Surveys Classifications of Interventions and Procedures-4 (OPCS-4) codes. Controls were matched to cases according to age, sex and socioeconomic status. Skin cancer data were obtained from linkage with other national data sources. Incidence was calculated per 100,000 person-years at risk (PYAR). Negative binomial regression was used to calculate adjusted incidence rate ratios (IRRs) for each organ type. During 2000-2018, 2,852 Welsh patients underwent solid organ transplantation. A total of 13,527 controls were matched from the general population. The incidence of skin cancer within the OTR cohort was 1203.2 per 100,000 PYAR vs 133.9 in the matched control group. Age, male gender and azathioprine use were all associated with an increased risk of skin cancer. Contemporary immunomodulators such as tacrolimus and mycophenolate were associated with a reduction in skin cancer risk when compared to their predecessors, cyclosporin and azathioprine. The highest adjusted IRR was observed in heart transplant recipients (IRR: 10.82; 95% CI: 3.64-32.19) and the lowest in liver transplant recipients (IRR: 2.86; 95% CI: 1.15-7.13). This study highlights the need for long-term routine skin cancer surveillance for all OTRs and the importance of using contemporary immunomodulators, when possible, for risk reduction.",,doi:https://doi.org/10.1684/ejd.2021.4108 +37225263,https://doi.org/10.1136/bmjgast-2023-001139,Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them.,"Kyriacou M, Radford S, Moran GW, Focus group collaborators group.",,BMJ open gastroenterology,2023,2023-05-01,Y,Ulcerative colitis; Inflammatory Bowel Disease; Adjuvant Treatment,,,"

Background

Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management.

Methods

A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements.

Results

In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision.

Conclusions

We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.",,doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render 33503030,https://doi.org/10.1371/journal.pone.0245636,Classification of road traffic injury collision characteristics using text mining analysis: Implications for road injury prevention.,"Giummarra MJ, Beck B, Gabbe BJ.",,PloS one,2021,2021-01-27,Y,,,,"Road traffic injuries are a leading cause of morbidity and mortality globally. Understanding circumstances leading to road traffic injury is crucial to improve road safety, and implement countermeasures to reduce the incidence and severity of road trauma. We aimed to characterise crash characteristics of road traffic collisions in Victoria, Australia, and to examine the relationship between crash characteristics and fault attribution. Data were extracted from the Victorian State Trauma Registry for motor vehicle drivers, motorcyclists, pedal cyclists and pedestrians with a no-fault compensation claim, aged > = 16 years and injured 2010-2016. People with intentional injury, serious head injury, no compensation claim/missing injury event description or who died < = 12-months post-injury were excluded, resulting in a sample of 2,486. Text mining of the injury event using QDA Miner and Wordstat was used to classify crash circumstances for each road user group. Crashes in which no other was at fault included circumstances involving lost control or avoiding a hazard, mechanical failure or medical conditions. Collisions in which another was predominantly at fault occurred at intersections with another vehicle entering from an adjacent direction, and head-on collisions. Crashes with higher prevalence of unknown fault included multi-vehicle collisions, pedal cyclists injured in rear-end collisions, and pedestrians hit while crossing the road or navigating slow traffic areas. We discuss several methods to promote road safety and to reduce the incidence and severity of road traffic injuries. Our recommendations take into consideration the incidence and impact of road trauma for different types of road users, and include engineering and infrastructure controls through to interventions targeting or accommodating human behaviour.",,doi:https://doi.org/10.1371/journal.pone.0245636; html:https://europepmc.org/articles/PMC7840051; pdf:https://europepmc.org/articles/PMC7840051?pdf=render +34427560,https://doi.org/10.1684/ejd.2021.4108,"The association between immunosuppression and skin cancer in solid organ transplant recipients: a control-matched cohort study of 2,852 patients.","Gibson JAG, Cordaro A, Dobbs TD, Griffiths R, Akbari A, Whitaker S, Hutchings HA, Lyons RA, Whitaker IS.",,European journal of dermatology : EJD,2021,2021-12-01,N,Transplant; Oncology; immunosuppression; Skin Cancer,,,"Skin cancer is more common in transplant recipients, although the quoted incidence is variable. This study investigated the incidence of skin cancer in solid organ transplant recipients (OTRs) in a national cohort and the effect of pharmacotherapeutic agents Transplant patients were identified from Patient Episode Database for Wales (PEDW) using Office of Population Census and Surveys Classifications of Interventions and Procedures-4 (OPCS-4) codes. Controls were matched to cases according to age, sex and socioeconomic status. Skin cancer data were obtained from linkage with other national data sources. Incidence was calculated per 100,000 person-years at risk (PYAR). Negative binomial regression was used to calculate adjusted incidence rate ratios (IRRs) for each organ type. During 2000-2018, 2,852 Welsh patients underwent solid organ transplantation. A total of 13,527 controls were matched from the general population. The incidence of skin cancer within the OTR cohort was 1203.2 per 100,000 PYAR vs 133.9 in the matched control group. Age, male gender and azathioprine use were all associated with an increased risk of skin cancer. Contemporary immunomodulators such as tacrolimus and mycophenolate were associated with a reduction in skin cancer risk when compared to their predecessors, cyclosporin and azathioprine. The highest adjusted IRR was observed in heart transplant recipients (IRR: 10.82; 95% CI: 3.64-32.19) and the lowest in liver transplant recipients (IRR: 2.86; 95% CI: 1.15-7.13). This study highlights the need for long-term routine skin cancer surveillance for all OTRs and the importance of using contemporary immunomodulators, when possible, for risk reduction.",,doi:https://doi.org/10.1684/ejd.2021.4108 35673545,https://doi.org/10.12688/wellcomeopenres.17231.2,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study.,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Simmons B, Klaber B, Elliott P, Darzi A, Riley S, Ashby D, Martin P, Gleeson S, Willicombe M, Kelleher P, Ward H, Barclay WS, Cooke GS.",,Wellcome open research,2021,2021-01-01,Y,Antibodies; Seroprevalence; Lateral Flow; Neutralisation; Lfia; Covid-19; Sars-cov-2,,,"Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.",,doi:https://doi.org/10.12688/wellcomeopenres.17231.2; html:https://europepmc.org/articles/PMC9152464; pdf:https://europepmc.org/articles/PMC9152464?pdf=render 34629034,https://doi.org/10.1080/02640414.2021.1928409,Are individual and social factors specific to the home associated with children's behaviour and physical environment at home.,"Sheldrick MPR, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,Journal of sports sciences,2021,2021-10-09,N,Youth; Family; House; Sedentary Time; Moderate-vigorous Physical Activity,,,"This study used linear regression analyses to investigate the influence of parent-reported home-specific social and individual factors on: (i) 235 children's home-based objectively measured overall sitting time, breaks in sitting, and PA, and; (ii) the home physical environment via an audit. Parental importance assigned to active play for children was positively associated with PA equipment (accessibility and availability), as well as light physical activity (LPA) and sitting breaks on both weekdays and weekend days. Parental preference for being active at home and limits on screen-time were associated with less household media equipment and portable media equipment, respectively. Greater parental importance placed on playing electronic games/using computers for fun was associated with less LPA and more sitting on weekdays. Further, children who preferred being sedentary sat more and engaged in less moderate-vigorous physical activity (MVPA) on weekdays. Parental and child preferences and priorities, as well as parental rules for activity at home, were associated with children's home-based sitting and PA, especially on weekdays. Such factors were also associated with the physical environment in the expected directions. The findings suggest interventions need to target social and individual factors, alongside adapting the physical environment to create homes more promotive of physical activity.",,doi:https://doi.org/10.1080/02640414.2021.1928409 -37223892,https://doi.org/10.1111/dme.15153,Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.,"Phillips K, Hazlehurst JM, Sheppard C, Bellary S, Hanif W, Karamat MA, Crowe FL, Stone A, Thomas GN, Peracha J, Fenton A, Sainsbury C, Nirantharakumar K, Dasgupta I.",,Diabetic medicine : a journal of the British Diabetic Association,2023,2023-05-24,N,Diabetes; Ethnicity; Inequality; Dkd,,,"

Aims

To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.

Methods

A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation.

Results

Of the 2.3 million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90 mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58 mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5 mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97).

Conclusions

There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.",,doi:https://doi.org/10.1111/dme.15153 33692093,https://doi.org/10.1136/heartjnl-2020-318557,Improving the diagnosis of heart failure in patients with atrial fibrillation.,"Bunting KV, Gill SK, Sitch A, Mehta S, O'Connor K, Lip GY, Kirchhof P, Strauss VY, Rahimi K, Camm AJ, Stanbury M, Griffith M, Townend JN, Gkoutos GV, Karwath A, Steeds RP, Kotecha D, RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial group.",,Heart (British Cardiac Society),2021,2021-03-10,Y,Atrial fibrillation; Echocardiography; Heart Failure; Systolic; Diastolic,,,"

Objective

To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval.

Methods

Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides.

Results

160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels.

Conclusions

Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.",,doi:https://doi.org/10.1136/heartjnl-2020-318557; html:https://europepmc.org/articles/PMC8142420; pdf:https://europepmc.org/articles/PMC8142420?pdf=render +37223892,https://doi.org/10.1111/dme.15153,Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.,"Phillips K, Hazlehurst JM, Sheppard C, Bellary S, Hanif W, Karamat MA, Crowe FL, Stone A, Thomas GN, Peracha J, Fenton A, Sainsbury C, Nirantharakumar K, Dasgupta I.",,Diabetic medicine : a journal of the British Diabetic Association,2023,2023-05-24,N,Diabetes; Ethnicity; Inequality; Dkd,,,"

Aims

To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.

Methods

A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation.

Results

Of the 2.3 million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90 mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58 mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5 mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97).

Conclusions

There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.",,doi:https://doi.org/10.1111/dme.15153 32896935,https://doi.org/10.1002/cbm.2166,Are Liaison and Diversion interventions in policing delivering the planned impact: A longitudinal evaluation in two constabularies?,"Kane E, Evans E, Mitsch J, Jilani T.",,Criminal behaviour and mental health : CBMH,2020,2020-09-08,N,Mental health; Outcomes; Offending; Policing; Liaison & Diversion,,,"Liaison and Diversion (L&D) has twin objectives: improving mental health outcomes and reducing re-offending. Early diversion from police custody seems promising, but evidence of benefit is required to sustain such programmes. To test the hypothesis that contact with L&D services while in police custody would lead to improved mental health outcomes and a reduction in type and level of offending, we used a pre-post service use design. National Health Service (NHS) records in two counties were searched for evidence that patients had been involved with L&D services while in police custody during the period July 2009-December 2017. We defined January 2009-July 2014 as the pre-intervention period and any time after contact as the post-intervention period. Data from the Police National Computer were gathered for each period for these individuals, to assess their pre-post L&D contact offending histories. NHS Trust data were similarly gathered to assess their pre-post use of mental health legislation. 4,462 individuals were identified who had used L&D services in police custody. There were statistically significant reductions in the amount of offending following contact with the L&D service (whether one or two contacts), regardless of offence type. Statistically significant reductions were also observed in use of the four most commonly used legislative powers for detaining patients in hospital on mental disorder grounds, regardless of offending status (prolific/non-prolific). Our results indicate positive associations between the L&D interventions and change in offending and use of compulsory hospital detention. Whilst our research does not allow a direct causal relationship to be established in either area, the findings go beyond other impact assessments of L&D which have either been with small samples or relied only on qualitative data or expert opinion.",,doi:https://doi.org/10.1002/cbm.2166 34610958,https://doi.org/10.1136/emermed-2019-209368,Association between anticoagulants and mortality and functional outcomes in older patients with major trauma. ,"Sato N, Cameron P, Mclellan S, Beck B, Gabbe B.",,Emergency medicine journal : EMJ,2021,2021-10-05,N,,,,"The number of trauma patients taking anticoagulants and antiplatelet agents is increasing as society ages. However, there have been limited and inconsistent reports of the association between anticoagulants and mortality and functional outcomes. This study aimed to quantify the association between anticoagulant/antiplatelet medication at the time of injury and both short-term and longer-term outcomes in older major trauma patients. This was a population-based registry study using data from the Victorian State Trauma Registry from July 2017 to June 2018. We included patients with major trauma aged 65 years and older. The outcomes of interest were in-hospital mortality, hospital length of stay, intensive care unit length of stay and the Extended Glasgow Outcome Scale (GOS-E) at 6 months after injury. We examined the association between the outcomes and anticoagulants/antiplatelet agents at the time of injury and used multivariable logistic regression models to account for known confounders. There were 1323 older adults eligible for inclusion in the study, of which 249 (18.8%) were taking anticoagulants (n=8 were taking both anticoagulants and antiplatelet agents), 380 (28.7%) were taking antiplatelet agents and 694 (52.5%) were not using either. Any anticoagulant use was associated with higher odds of in-hospital mortality (adjusted OR (AOR), 2.38; 95% CI 1.58 to 3.59) compared with not using anticoagulants. No differences were observed in the GOS-E at 6 months after injury between any anticoagulants use, antiplatelet use and no anticoagulant use (anticoagulant AOR, 0.71; 95% CI 0.48 to 1.05, antiplatelet AOR, 1.02; 95% CI 0.73 to 1.42). Anticoagulant use at the time of injury was associated with higher odds of in-hospital mortality but did not adversely impact functional outcomes at 6 months after injury. These findings demonstrate the importance of seeking an accurate history of anticoagulant use and its indication, as well as the immediate initiation of reversal therapies.",,doi:https://doi.org/10.1136/emermed-2019-209368 -36426221,https://doi.org/10.3389/fcvm.2022.1016032,Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging.,"Szabo L, Raisi-Estabragh Z, Salih A, McCracken C, Ruiz Pujadas E, Gkontra P, Kiss M, Maurovich-Horvath P, Vago H, Merkely B, Lee AM, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2022,2022-11-08,Y,Artificial intelligence; Trustworthiness; Cardiovascular Imaging; Machine Learning (Ml); Ai Risk,,,"A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their ""trustworthiness"" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a ""trustworthy AI system."" We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.",,doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?pdf=render 35151869,https://doi.org/10.1016/j.jbi.2022.104010,Patient-centric characterization of multimorbidity trajectories in patients with severe mental illnesses: A temporal bipartite network modeling approach.,"Wang T, Bendayan R, Msosa Y, Pritchard M, Roberts A, Stewart R, Dobson R.",,Journal of biomedical informatics,2022,2022-02-11,Y,Network Evolution; Multimorbidity; Severe Mental Illnesses; Disease Trajectories; Ehr Data Linkage; Temporal Bipartite Network,,,"Multimorbidity is a major factor contributing to increased mortality among people with severe mental illnesses (SMI). Previous studies either focus on estimating prevalence of a disease in a population without considering relationships between diseases or ignore heterogeneity of individual patients in examining disease progression by looking merely at aggregates across a whole cohort. Here, we present a temporal bipartite network model to jointly represent detailed information on both individual patients and diseases, which allows us to systematically characterize disease trajectories from both patient and disease centric perspectives. We apply this approach to a large set of longitudinal diagnostic records for patients with SMI collected through a data linkage between electronic health records from a large UK mental health hospital and English national hospital administrative database. We find that the resulting diagnosis networks show disassortative mixing by degree, suggesting that patients affected by a small number of diseases tend to suffer from prevalent diseases. Factors that determine the network structures include an individual's age, gender and ethnicity. Our analysis on network evolution further shows that patients and diseases become more interconnected over the illness duration of SMI, which is largely driven by the process that patients with similar attributes tend to suffer from the same conditions. Our analytic approach provides a guide for future patient-centric research on multimorbidity trajectories and contributes to achieving precision medicine.",,doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882 +36426221,https://doi.org/10.3389/fcvm.2022.1016032,Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging.,"Szabo L, Raisi-Estabragh Z, Salih A, McCracken C, Ruiz Pujadas E, Gkontra P, Kiss M, Maurovich-Horvath P, Vago H, Merkely B, Lee AM, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2022,2022-11-08,Y,Artificial intelligence; Trustworthiness; Cardiovascular Imaging; Machine Learning (Ml); Ai Risk,,,"A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their ""trustworthiness"" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a ""trustworthy AI system."" We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.",,doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?pdf=render 32728709,https://doi.org/10.1093/pubmed/fdaa115,Are children who are home from school at an increased risk of child maltreatment?,"Syed S, Gilbert R.",,"Journal of public health (Oxford, England)",2021,2021-04-01,N,,,,,,doi:https://doi.org/10.1093/pubmed/fdaa115 34939031,https://doi.org/10.1093/braincomms/fcab241,Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.,"Vuksanović V, Staff RT, Morson S, Ahearn T, Bracoud L, Murray AD, Bentham P, Kipps CM, Harrington CR, Wischik CM.",,Brain communications,2021,2021-10-21,Y,Neurodegeneration; Brain Networks; Behavioural Variant Frontotemporal Dementia; Rich Club; Anatomical Subtypes,,,"The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.",,doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render 35440465,https://doi.org/10.3399/bjgp.2021.0689,Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.,"Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19,,,"

Background

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

Aim

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

Design and setting

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

Method

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

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.",,doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render @@ -907,16 +910,16 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 31398202,https://doi.org/10.1371/journal.pone.0220771,The role of health and social factors in education outcome: A record-linked electronic birth cohort analysis.,"Evans A, Dunstan F, Fone DL, Bandyopadhyay A, Schofield B, Demmler JC, Rahman MA, Lyons RA, Paranjothy S.",,PloS one,2019,2019-08-09,Y,,Improving Public Health,,"

Background and objective

Health status in childhood is correlated with educational outcomes. Emergency hospital admissions during childhood are common but it is not known how these unplanned breaks from schooling impact on education outcomes. We hypothesised that children who had emergency hospital admissions had an increased risk of lower educational attainment, in addition to the increased risks associated with other health, social and school factors.

Methods

This record-linked electronic birth cohort, included children born in Wales between 1 January 1998 and 31 August 2001. We fitted multilevel logistic regression models grouped by schools, to determine whether emergency hospital inpatient admission before age 7 years was associated with the educational outcome of not attaining the expected level in a teacher-based assessment at age 7 years (KS1). We adjusted for pregnancy, perinatal, socio-economic, neighbourhood, pupil mobility and school-level factors.

Results

The cohort comprised 64 934 children. Overall, 4680 (7.2%) did not attain the expected educational level. Emergency admission to hospital was associated with poor educational attainment (OR 1.12 95% Credible Interval (CI) 1.05, 1.20 for all causes during childhood, OR 1.19 95%CI 1.07, 1.32 for injuries and external causes and OR 1.31 95%CI 1.04, 1.22 for admissions during infancy), after adjusting for known determinants of education outcomes such as extreme prematurity, being small for gestational age and socio-economic indicators, such as eligibility for free school meals.

Conclusion

Emergency inpatient hospital admission during childhood, particularly during infancy or for injuries and external causes was associated with an increased risk of lower education attainment at age 7 years, in addition to the effects of pregnancy factors (gestational age, birthweight) and social deprivation. These findings support the need for injury prevention measures and additional support in school for affected children to help them to achieve their potential.",,doi:https://doi.org/10.1371/journal.pone.0220771; html:https://europepmc.org/articles/PMC6688802; pdf:https://europepmc.org/articles/PMC6688802?pdf=render 34631820,https://doi.org/10.3389/fcvm.2021.716577,New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.,"Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-09-23,Y,Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis,,,"Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",,doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render 34871122,https://doi.org/10.1080/09638288.2021.2008526,Pain and mental health symptom patterns and treatment trajectories following road trauma: a registry-based cohort study.,"Huang S, Dipnall JF, Gabbe BJ, Giummarra MJ.",,Disability and rehabilitation,2022,2021-12-06,N,Injury; Recovery; Pain; Mental health; Healthcare Use,,,"

Purpose

This study aimed to characterise recovery from pain and mental health symptoms, and identify whether treatment use facilitates recovery.

Methods

Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry participants without neurotrauma who had transport injury claims with the Transport Accident Commission from 2007 to 2014 were included (n = 5908). Latent transition analysis of pain Numeric Rating Scale, SF-12, and EQ-5D-3L pain and mental health items from 6 to 12 months, and 12 to 24 months post-injury were used to identify symptom transitions.

Results

Four transition groups were identified: transition to low problems by 12-months; transition to low problems at 24-months; stable low problems; and no transition from problems. Group-based trajectory modelling of pain and mental health treatments found three treatment trajectories: low/no treatment, a moderate treatment that declined to low treatment 3-12 months post-injury, and increasing treatment over time. Predictors of pain and mental health recovery transitions, identified using multinomial logistic regression, were primarily found to be non-modifiable socioeconomic and health-related characteristics (e.g., higher education, working pre-injury, and not having comorbidities), and low treatment trajectories.

Conclusions

Targeted and collaborative rehabilitation should be considered for people at risk of persistent pain or mental health symptoms to optimise their recovery, particularly patients with socioeconomic disadvantage.IMPLICATIONS FOR REHABILITATIONTwo-thirds of people experience pain and/or mental health within the first 24-months after hospitalization for road trauma, of whom only 6-7% recover by 12-months, and a further 6% recover by 24-months post-injury.There were three main trajectories of administrative records of treatments received in the first two years after injury: 76 and 83% had low treatment, 18 and 12% had moderate then declining treatment levels, and 6 and 5% had stable high treatment for pain or mental health, respectively.People who recovered from pain or mental health symptoms generally had lower treatment and higher socioeconomic position, highlighting that coordinated rehabilitation care should be prioritized for people living with socioeconomic disadvantage.",,doi:https://doi.org/10.1080/09638288.2021.2008526 -36660920,https://doi.org/10.1093/ehjci/jeac270,The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.,"Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-06-01,Y,Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes,,,"

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.",,doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render 33820530,https://doi.org/10.1186/s12916-021-01940-7,"Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility.","Banerjee A, Chen S, Fatemifar G, Zeina M, Lumbers RT, Mielke J, Gill S, Kotecha D, Freitag DF, Denaxas S, Hemingway H.",,BMC medicine,2021,2021-04-06,Y,Subtype; Cardiovascular disease; Systematic review; Machine Learning; Informatics; Risk Prediction,,,"

Background

Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF).

Methods

For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist.

Results

Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations).

Conclusions

Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.",,doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render; pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7 +36660920,https://doi.org/10.1093/ehjci/jeac270,The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.,"Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-06-01,Y,Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes,,,"

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.",,doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render 34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render 33707775,https://doi.org/10.1038/s41591-021-01266-0,Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.,"Pietzner M, Stewart ID, Raffler J, Khaw KT, Michelotti GA, Kastenmüller G, Wareham NJ, Langenberg C.",,Nature medicine,2021,2021-03-11,N,,,,"Multimorbidity, the simultaneous presence of multiple chronic conditions, is an increasing global health problem and research into its determinants is of high priority. We used baseline untargeted plasma metabolomics profiling covering >1,000 metabolites as a comprehensive readout of human physiology to characterize pathways associated with and across 27 incident noncommunicable diseases (NCDs) assessed using electronic health record hospitalization and cancer registry data from over 11,000 participants (219,415 person years). We identified 420 metabolites shared between at least 2 NCDs, representing 65.5% of all 640 significant metabolite-disease associations. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways represented by those metabolites. Our study highlights liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity and specific health-related behaviors as antecedents of common NCD multimorbidity with potential for early prevention. We integrated results into an open-access webserver ( https://omicscience.org/apps/mwasdisease/ ) to facilitate future research and meta-analyses.",,doi:https://doi.org/10.1038/s41591-021-01266-0; html:https://europepmc.org/articles/PMC8127079; pdf:https://europepmc.org/articles/PMC8127079?pdf=render; doi:https://doi.org/10.1038/s41591-021-01266-0 34912046,https://doi.org/10.1038/s41366-021-01048-1,"30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data.","Singhal R, Cardoso VR, Wiggins T, Super J, Ludwig C, Gkoutos GV, Mahawar K, GENEVA Collaborators.",,International journal of obesity (2005),2022,2021-12-15,Y,,,,"

Background

There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts.

Materials and methods

This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien-Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups.

Results

In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07).

Conclusions

This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.",,doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render; pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf 34053271,https://doi.org/10.1098/rstb.2020.0266,Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection.,"Jombart T, Ghozzi S, Schumacher D, Taylor TJ, Leclerc QJ, Jit M, Flasche S, Greaves F, Ward T, Eggo RM, Nightingale E, Meakin S, Brady OJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley GF, Höhle M, Edmunds WJ.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Algorithm; Surveillance; outbreak; Machine Learning; Asmodee; Trendbreaker,,,"As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0266; html:https://europepmc.org/articles/PMC8165581; pdf:https://europepmc.org/articles/PMC8165581?pdf=render 36194451,https://doi.org/10.2196/40667,Associations Between Depression Symptom Severity and Daily-Life Gait Characteristics Derived From Long-Term Acceleration Signals in Real-World Settings: Retrospective Analysis.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Qian L, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,JMIR mHealth and uHealth,2022,2022-10-04,Y,Monitoring; Depression; Gait; Mental health; Mobile Phones; Mhealth; Mobile Health; Wearable Devices; Acceleration Signals,,,"

Background

Gait is an essential manifestation of depression. However, the gait characteristics of daily walking and their relationships with depression have yet to be fully explored.

Objective

The aim of this study was to explore associations between depression symptom severity and daily-life gait characteristics derived from acceleration signals in real-world settings.

Methods

We used two ambulatory data sets (N=71 and N=215) with acceleration signals collected by wearable devices and mobile phones, respectively. We extracted 12 daily-life gait features to describe the distribution and variance of gait cadence and force over a long-term period. Spearman coefficients and linear mixed-effects models were used to explore the associations between daily-life gait features and depression symptom severity measured by the 15-item Geriatric Depression Scale (GDS-15) and 8-item Patient Health Questionnaire (PHQ-8) self-reported questionnaires. The likelihood-ratio (LR) test was used to test whether daily-life gait features could provide additional information relative to the laboratory gait features.

Results

Higher depression symptom severity was significantly associated with lower gait cadence of high-performance walking (segments with faster walking speed) over a long-term period in both data sets. The linear regression model with long-term daily-life gait features (R2=0.30) fitted depression scores significantly better (LR test P=.001) than the model with only laboratory gait features (R2=0.06).

Conclusions

This study indicated that the significant links between daily-life walking characteristics and depression symptom severity could be captured by both wearable devices and mobile phones. The daily-life gait patterns could provide additional information for predicting depression symptom severity relative to laboratory walking. These findings may contribute to developing clinical tools to remotely monitor mental health in real-world settings.",,doi:https://doi.org/10.2196/40667; html:https://europepmc.org/articles/PMC9579931 37230417,https://doi.org/10.1016/j.jtha.2023.05.012,C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.,"Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-05-23,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.05.012 -37218687,https://doi.org/10.1093/ehjqcco/qcad029,Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.,"Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Quality of care & clinical outcomes,2023,2023-05-22,N,Myocardial infarction; Stroke; Sex differences; risk factors,,,"

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363 313 participants (53.5% women), 8 470 experienced MI (29.9% women) and 7 705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.",,doi:https://doi.org/10.1093/ehjqcco/qcad029; pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf 33678589,https://doi.org/10.1016/s2589-7500(20)30317-4,Health data poverty: an assailable barrier to equitable digital health care.,"Ibrahim H, Liu X, Zariffa N, Morris AD, Denniston AK.",,The Lancet. Digital health,2021,2021-03-04,N,,,,"Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.",,doi:https://doi.org/10.1016/S2589-7500(20)30317-4 +37218687,https://doi.org/10.1093/ehjqcco/qcad029,Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.,"Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Quality of care & clinical outcomes,2023,2023-05-22,N,Myocardial infarction; Stroke; Sex differences; risk factors,,,"

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363 313 participants (53.5% women), 8 470 experienced MI (29.9% women) and 7 705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.",,doi:https://doi.org/10.1093/ehjqcco/qcad029; pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf 35589356,https://doi.org/10.1136/bmjopen-2021-057343,"Linkage of National Congenital Heart Disease Audit data to hospital, critical care and mortality national data sets to enable research focused on quality improvement.","Espuny Pujol F, Pagel C, Brown KL, Doidge JC, Feltbower RG, Franklin RC, Gonzalez-Izquierdo A, Gould DW, Norman LJ, Stickley J, Taylor JA, Crowe S.",,BMJ open,2022,2022-05-19,Y,Congenital heart disease; Audit; Health Informatics; Statistics & Research Methods; Quality In Health Care,,,"

Objectives

To link five national data sets (three registries, two administrative) and create longitudinal healthcare trajectories for patients with congenital heart disease (CHD), describing the quality and the summary statistics of the linked data set.

Design

Bespoke linkage of record-level patient identifiers across five national data sets. Generation of spells of care defined as periods of time-overlapping events across the data sets.

Setting

National Congenital Heart Disease Audit (NCHDA) procedures in public (National Health Service; NHS) hospitals in England and Wales, paediatric and adult intensive care data sets (Paediatric Intensive Care Audit Network; PICANet and the Case Mix Programme from the Intensive Care National Audit & Research Centre; ICNARC-CMP), administrative hospital episodes (hospital episode statistics; HES inpatient, outpatient, accident and emergency; A&E) and mortality registry data.

Participants

Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals.

Primary and secondary outcome measures

Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage.

Results

There were 143 862 records in NCHDA relating to 96 041 unique patients. We identified 65 797 linked PICANet patient admissions, 4664 linked ICNARC-CMP admissions and over 6 million linked HES episodes of care (1.1M inpatient, 4.7M outpatient). The linked data set had 4 908 153 spells of care after quality checks, with a median (IQR) of 3.4 (1.8-6.3) spells per patient-year. Where linkage was feasible (in terms of year and centre), 95.6% surgical procedure records were linked to a corresponding HES record, 93.9% paediatric (cardiac) surgery procedure records to a corresponding PICANet admission and 76.8% adult surgery procedure records to a corresponding ICNARC-CMP record.

Conclusions

We successfully linked four national data sets to the core data set of all CHD procedures performed between 2000 and 2017. This will enable a much richer analysis of longitudinal patient journeys and outcomes. We hope that our detailed description of the linkage process will be useful to others looking to link national data sets to address important research priorities.",,doi:https://doi.org/10.1136/bmjopen-2021-057343; html:https://europepmc.org/articles/PMC9121475; pdf:https://europepmc.org/articles/PMC9121475?pdf=render 37133927,https://doi.org/10.2196/45534,"Understanding Views Around the Creation of a Consented, Donated Databank of Clinical Free Text to Develop and Train Natural Language Processing Models for Research: Focus Group Interviews With Stakeholders.","Fitzpatrick NK, Dobson R, Roberts A, Jones K, Shah AD, Nenadic G, Ford E.",,JMIR medical informatics,2023,2023-05-03,Y,Consent; Governance; Electronic Health Records; Natural Language Processing; Free Text; Databank; Public Involvement; Unstructured Text,,,"

Background

Information stored within electronic health records is often recorded as unstructured text. Special computerized natural language processing (NLP) tools are needed to process this text; however, complex governance arrangements make such data in the National Health Service hard to access, and therefore, it is difficult to use for research in improving NLP methods. The creation of a donated databank of clinical free text could provide an important opportunity for researchers to develop NLP methods and tools and may circumvent delays in accessing the data needed to train the models. However, to date, there has been little or no engagement with stakeholders on the acceptability and design considerations of establishing a free-text databank for this purpose.

Objective

This study aimed to ascertain stakeholder views around the creation of a consented, donated databank of clinical free text to help create, train, and evaluate NLP for clinical research and to inform the potential next steps for adopting a partner-led approach to establish a national, funded databank of free text for use by the research community.

Methods

Web-based in-depth focus group interviews were conducted with 4 stakeholder groups (patients and members of the public, clinicians, information governance leads and research ethics members, and NLP researchers).

Results

All stakeholder groups were strongly in favor of the databank and saw great value in creating an environment where NLP tools can be tested and trained to improve their accuracy. Participants highlighted a range of complex issues for consideration as the databank is developed, including communicating the intended purpose, the approach to access and safeguarding the data, who should have access, and how to fund the databank. Participants recommended that a small-scale, gradual approach be adopted to start to gather donations and encouraged further engagement with stakeholders to develop a road map and set of standards for the databank.

Conclusions

These findings provide a clear mandate to begin developing the databank and a framework for stakeholder expectations, which we would aim to meet with the databank delivery.",,doi:https://doi.org/10.2196/45534; html:https://europepmc.org/articles/PMC10193205 37124165,https://doi.org/10.1016/j.ufug.2023.127934,"Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.","Hajna S, Cummins S.",,Urban forestry & urban greening,2023,2023-04-11,Y,Parks; Crimes; Covid-19,,,"

Introduction

Park crimes may have increased during the COVID-19 pandemic as a result of lockdowns that limited the number of capable guardians in public spaces. Despite this, the impacts of the lockdowns on park crimes remain unknown. To help us understand the societal impacts of policies implemented during this period, we assessed how the onset of the COVID-19 restrictions impacted urban park crime levels in London, England.

Methods

We identified crimes that occurred in publicly accessible parks and gardens in the Greater London Authority (England, UK) between March 1, 2019 and February 28, 2021 by overlaying open-access crime data with greenspace data supplied by the Greater Information for Greater London service. Using interrupted time series analyses, we estimated seasonality-adjusted associations between the onset of COVID-19 restrictions and park crimes.

Results

Overall (1565.7, 95% confidence intervals [CI] 1021.9 to 2109.5) and antisocial behaviour crimes (1772.7, 95% CI 823.6-2721.7) increased in London parks during the first full month of COVID-19 restrictions (April 2020). There were no notable trends in park crimes in London prior to the onset of restrictions, but overall and antisocial behaviour crimes decreased after the onset of restrictions at a rate of 156.4 (95% CI -220.25 to -92.51) and 164.7 (95% CI -280.68 to -48.74) crimes/months, respectively.

Conclusions

Overall park crimes increased during the first full month of the COVID-19 restrictions, largely driven by an increase in antisocial behaviours. Additional research is needed to identify the specific misdemeanours that accounted for this rise in antisocial behaviours and to investigate their downstream impacts (e.g. increases in policing costs or decreases in perceived park safety).",,doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render @@ -944,16 +947,16 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 36357675,https://doi.org/10.1038/s41591-022-02046-0,Rare and common genetic determinants of metabolic individuality and their effects on human health.,"Surendran P, Stewart ID, Au Yeung VPW, Pietzner M, Raffler J, Wörheide MA, Li C, Smith RF, Wittemans LBL, Bomba L, Menni C, Zierer J, Rossi N, Sheridan PA, Watkins NA, Mangino M, Hysi PG, Di Angelantonio E, Falchi M, Spector TD, Soranzo N, Michelotti GA, Arlt W, Lotta LA, Denaxas S, Hemingway H, Gamazon ER, Howson JMM, Wood AM, Danesh J, Wareham NJ, Kastenmüller G, Fauman EB, Suhre K, Butterworth AS, Langenberg C.",,Nature medicine,2022,2022-11-10,Y,,,,"Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.25 × 10-11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant-metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.",,doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render 36137640,https://doi.org/10.1136/bmjopen-2022-064586,Myocardial infarction and stroke subsequent to urinary tract infection (MISSOURI): protocol for a self-controlled case series using linked electronic health records.,"Reeve NF, Best V, Gillespie D, Hughes K, Lugg-Widger FV, Cannings-John R, Torabi F, Wootton M, Akbari A, Ahmed H.",,BMJ open,2022,2022-09-22,Y,Myocardial infarction; Stroke; Urinary tract infections,,,"

Introduction

There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke.

Methods and analysis

We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010-2020. Individuals will need to be aged 30-100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in 'baseline' periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios.

Ethics and dissemination

Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.",,doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render 33990383,https://doi.org/10.1136/gutjnl-2020-323546,Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.,"Curtius K, Kabir M, Al Bakir I, Choi CHR, Hartono JL, Johnson M, East JE, Oxford IBD Cohort Study Investigators, Lindsay JO, Vega R, Thomas-Gibson S, Warusavitarne J, Wilson A, Graham TA, Hart A.",,Gut,2022,2021-05-14,Y,Dysplasia; Ulcerative colitis; Colorectal Cancer; Clinical Decision Making,,,"

Objective

Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk.

Design

In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk.

Results

Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.

Conclusion

Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.",,doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render -37198478,https://doi.org/10.1038/s41586-023-06034-3,GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.,"Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.",,Nature,2023,2023-05-17,Y,,,,"Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).",,doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render; pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf 32771960,https://doi.org/10.1016/j.ijmedinf.2020.104237,Core competencies for clinical informaticians: A systematic review.,"Davies A, Mueller J, Moulton G.",,International journal of medical informatics,2020,2020-07-24,N,Bioinformatics; Health; Clinical; Pharmacy; Skills; Informatics; Requirements; Core Competencies; Healthcare Data Science,,,"

Background

Building on initial work carried out by the Faculty of Clinical Informatics (FCI) in the UK, the creation of a national competency framework for Clinical Informatics is required for the definition of clinical informaticians' professional attributes and skills. We aimed to systematically review the academic literature relating to competencies, skills and existing course curricula in the clinical and health related informatics domains.

Methods

Two independent reviewers searched Web of Science, EMBASE, ERIC, PubMed and CINAHL. Publications were included if they reported details of relevant competencies, skills and existing course curricula. We report findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

Results

A total of 82 publications were included. The most frequently used method was surveys (30 %) followed by narrative descriptions (28 %). Most of the publications describe curriculum design (23 %) followed by competency definition (18 %) and skills, qualifications & training (18 %). Core skills surrounding data, information systems and information management appear to be cross-cutting across the various informatics disciplines with Bioinformatics and Pharmacy Informatics expressing the most unique competency requirements.

Conclusion

We identified eight key domains that cut across the different sub-disciplines of health informatics, including data, information management, human factors, project management, research skills/knowledge, leadership and management, systems development and evaluation, and health/healthcare. Some informatics disciplines such as Nursing Informatics appear to be further ahead at achieving widespread competency standardisation. Attempts at standardisation for competencies should be tempered with flexibility to allow for local variation and requirements.",,doi:https://doi.org/10.1016/j.ijmedinf.2020.104237 33328049,https://doi.org/10.1016/s2589-7500(20)30219-3,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the design and risk of bias for a planned clinical trial.",,doi:https://doi.org/10.1016/S2589-7500(20)30219-3; html:https://europepmc.org/articles/PMC8212701; pdf:https://europepmc.org/articles/PMC8212701?pdf=render +37198478,https://doi.org/10.1038/s41586-023-06034-3,GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.,"Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.",,Nature,2023,2023-05-17,Y,,,,"Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).",,doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render; pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf 36545688,https://doi.org/10.1192/bjb.2022.83,EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.,"Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivières S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",,BJPsych bulletin,2022,2022-12-22,N,Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working,,,"EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",,doi:https://doi.org/10.1192/bjb.2022.83 37286615,https://doi.org/10.1038/s41598-023-36214-0,Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank.,"Liu X, Morelli D, Littlejohns TJ, Clifton DA, Clifton L.",,Scientific reports,2023,2023-06-07,Y,,,,"We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An ""extreme gradient boosting"" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among [Formula: see text] 1.7 k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the ""augmented"" Cox model (incorporating the two PRS, known and novel predictors) with a ""baseline"" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ([Formula: see text]). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR = 0.95, 95% CI 0.92-0.98, [Formula: see text]), plasma phosphate (HR = 0.68, 95% CI 0.53-0.88, [Formula: see text]), basal metabolic rate (HR = 1.17, 95% CI 1.11-1.24, [Formula: see text]), red blood cell count (HR = 1.21, 95% CI 1.08-1.35, [Formula: see text]), and creatinine in urine (HR = 1.05, 95% CI 1.01-1.09, [Formula: see text]). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.",,doi:https://doi.org/10.1038/s41598-023-36214-0; html:https://europepmc.org/articles/PMC10247810; pdf:https://europepmc.org/articles/PMC10247810?pdf=render 37285143,https://doi.org/10.1001/jamacardio.2023.1290,Diagnostic and Prognostic Value of Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis.,"Ricci F, Khanji MY, Bisaccia G, Cipriani A, Di Cesare A, Ceriello L, Mantini C, Zimarino M, Fedorowski A, Gallina S, Petersen SE, Bucciarelli-Ducci C.",,JAMA cardiology,2023,2023-07-01,N,,,,"

Importance

The clinical utility of stress cardiovascular magnetic resonance imaging (CMR) in stable chest pain is still debated, and the low-risk period for adverse cardiovascular (CV) events after a negative test result is unknown.

Objective

To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain.

Data sources

PubMed and Embase databases, the Cochrane Database of Systematic Reviews, PROSPERO, and the ClinicalTrials.gov registry were searched for potentially relevant articles from January 1, 2000, through December 31, 2021.

Study selection

Selected studies evaluated CMR and reported estimates of diagnostic accuracy and/or raw data of adverse CV events for participants with either positive or negative stress CMR results. Prespecified combinations of keywords related to the diagnostic accuracy and prognostic value of stress CMR were used. A total of 3144 records were evaluated for title and abstract; of those, 235 articles were included in the full-text assessment of eligibility. After exclusions, 64 studies (74 470 total patients) published from October 29, 2002, through October 19, 2021, were included.

Data extraction and synthesis

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Main outcomes and measures

Diagnostic odds ratios (DORs), sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), odds ratio (OR), and annualized event rate (AER) for all-cause death, CV death, and major adverse cardiovascular events (MACEs) defined as the composite of myocardial infarction and CV death.

Results

A total of 33 diagnostic studies pooling 7814 individuals and 31 prognostic studies pooling 67 080 individuals (mean [SD] follow-up, 3.5 [2.1] years; range, 0.9-8.8 years; 381 357 person-years) were identified. Stress CMR yielded a DOR of 26.4 (95% CI, 10.6-65.9), a sensitivity of 81% (95% CI, 68%-89%), a specificity of 86% (95% CI, 75%-93%), and an AUROC of 0.84 (95% CI, 0.77-0.89) for the detection of functionally obstructive coronary artery disease. In the subgroup analysis, stress CMR yielded higher diagnostic accuracy in the setting of suspected coronary artery disease (DOR, 53.4; 95% CI, 27.7-103.0) or when using 3-T imaging (DOR, 33.2; 95% CI, 19.9-55.4). The presence of stress-inducible ischemia was associated with higher all-cause mortality (OR, 1.97; 95% CI, 1.69-2.31), CV mortality (OR, 6.40; 95% CI, 4.48-9.14), and MACEs (OR, 5.33; 95% CI, 4.04-7.04). The presence of late gadolinium enhancement (LGE) was associated with higher all-cause mortality (OR, 2.22; 95% CI, 1.99-2.47), CV mortality (OR, 6.03; 95% CI, 2.76-13.13), and increased risk of MACEs (OR, 5.42; 95% CI, 3.42-8.60). After a negative test result, pooled AERs for CV death were less than 1.0%.

Conclusion and relevance

In this study, stress CMR yielded high diagnostic accuracy and delivered robust prognostication, particularly when 3-T scanners were used. While inducible myocardial ischemia and LGE were associated with higher mortality and risk of MACEs, normal stress CMR results were associated with a lower risk of MACEs for at least 3.5 years.",,doi:https://doi.org/10.1001/jamacardio.2023.1290 37438684,https://doi.org/10.1186/s12874-023-01935-3,Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.,"Tibble H, Sheikh A, Tsanas A.",,BMC medical research methodology,2023,2023-07-12,Y,Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records,,,"

Background

Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.

Methods

Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.

Results

Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.

Conclusions

We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",,doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render; pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3 +33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Swab Test; Covid-19,,,"Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render 37634573,https://doi.org/10.1016/j.cardfail.2023.08.008,Does Heterogeneity Exist in Treatment Associations with Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?,"Uijl A, Koudstaal S, Stolfo D, Dahlström U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, Savarese G.",,Journal of cardiac failure,2023,2023-08-25,N,Personalized Medicine; Beta-blockers; Hfpef; Phenotype Clusters; Renin-angiotensin-system Inhibitors,,,"

Aims

To explore the association between use of renin-angiotensin-system inhibitors (RASi) and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure and preserved ejection fraction (HFpEF).

Methods and results

We analysed 20,980 HFpEF patients from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation (AF)-hypertensive (32%), older-AF (24%), obese-diabetic (15%) and a cardio-renal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between RASi use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (p-value 0.03) and non-CV hospitalisation (p-value 0.001). In the young-low comorbidity burden and AF-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients improved ejection fraction. However, patient numbers were diminished when excluding those with improved ejection fraction and the direction of the associations remained similar.

Conclusion

In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.",,doi:https://doi.org/10.1016/j.cardfail.2023.08.008 36648036,https://doi.org/10.1016/j.jcmg.2022.06.011,Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank.,"Raisi-Estabragh Z, McCracken C, Hann E, Condurache DG, Harvey NC, Munroe PB, Ferreira VM, Neubauer S, Piechnik SK, Petersen SE.",,JACC. Cardiovascular imaging,2023,2022-09-14,Y,Mortality; Cardiovascular disease; Cardiac Magnetic Resonance; Native T1 Mapping; Incident Events,,,"

Background

Cardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.

Objectives

The associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.

Methods

Native T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.

Results

Higher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).

Conclusions

This large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.",,doi:https://doi.org/10.1016/j.jcmg.2022.06.011; html:https://europepmc.org/articles/PMC10102720; pdf:https://europepmc.org/articles/PMC10102720?pdf=render -33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Swab Test; Covid-19,,,"Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render 34230034,https://doi.org/10.1136/bmjresp-2021-000967,Increase in recruitment upon integration of trial into a clinical care pathway: an observational study. ,"Yip KP, Gompertz S, Snelson C, Willson J, Madathil S, Huq SS, Rauf F, Salmon N, Tengende J, Tracey J, Cooper B, Filby K, Ball S, Parekh D, Dosanjh DPS.",,BMJ open respiratory research,2021,2021-07-01,Y,,,,"Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers. A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP. On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence. Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.",,doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render 30279426,https://doi.org/10.1038/s41598-018-32876-3,OligoPVP: Phenotype-driven analysis of individual genomic information to prioritize oligogenic disease variants.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,Scientific reports,2018,2018-10-02,Y,,"Applied Analytics, The Human Phenome",,"An increasing number of disorders have been identified for which two or more distinct alleles in two or more genes are required to either cause the disease or to significantly modify its onset, severity or phenotype. It is difficult to discover such interactions using existing approaches. The purpose of our work is to develop and evaluate a system that can identify combinations of alleles underlying digenic and oligogenic diseases in individual whole exome or whole genome sequences. Information that links patient phenotypes to databases of gene-phenotype associations observed in clinical or non-human model organism research can provide useful information and improve variant prioritization for genetic diseases. Additional background knowledge about interactions between genes can be utilized to identify sets of variants in different genes in the same individual which may then contribute to the overall disease phenotype. We have developed OligoPVP, an algorithm that can be used to prioritize causative combinations of variants in digenic and oligogenic diseases, using whole exome or whole genome sequences together with patient phenotypes as input. We demonstrate that OligoPVP has significantly improved performance when compared to state of the art pathogenicity detection methods in the case of digenic diseases. Our results show that OligoPVP can efficiently prioritize sets of variants in digenic diseases using a phenotype-driven approach and identify etiologically important variants in whole genomes. OligoPVP naturally extends to oligogenic disease involving interactions between variants in two or more genes. It can be applied to the identification of multiple interacting candidate variants contributing to phenotype, where the action of modifier genes is suspected from pedigree analysis or failure of traditional causative variant identification.",,doi:https://doi.org/10.1038/s41598-018-32876-3; html:https://europepmc.org/articles/PMC6168481; pdf:https://europepmc.org/articles/PMC6168481?pdf=render; pdf:https://www.nature.com/articles/s41598-018-32876-3.pdf 31442537,https://doi.org/10.1016/j.jaad.2019.08.039,Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.,"Schmidt SAJ, Olsen M, Schmidt M, Vestergaard C, Langan SM, Deleuran MS, Riis JL.",,Journal of the American Academy of Dermatology,2020,2019-08-20,Y,Validation; Atrial fibrillation; Atrial flutter; Cohort study; risk factors; Atopic Dermatitis,Understanding the Causes of Disease,,"

Background

Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation.

Objective

To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation.

Methods

Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review.

Results

We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors.

Limitations

Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data.

Conclusion

Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.",,doi:https://doi.org/10.1016/j.jaad.2019.08.039; html:https://europepmc.org/articles/PMC7704103; pdf:https://europepmc.org/articles/PMC7704103?pdf=render @@ -963,8 +966,8 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 36224187,https://doi.org/10.1038/s41467-022-33826-4,Key considerations to reduce or address respondent burden in patient-reported outcome (PRO) data collection.,"Aiyegbusi OL, Roydhouse J, Rivera SC, Kamudoni P, Schache P, Wilson R, Stephens R, Calvert M.",,Nature communications,2022,2022-10-12,Y,,,,"Patient-reported outcomes (PROs) are used in clinical trials to provide evidence of the benefits and risks of interventions from a patient perspective and to inform regulatory decisions and health policy. The collection of PROs in routine practice can facilitate monitoring of patient symptoms; identification of unmet needs; prioritisation and/or tailoring of treatment to the needs of individual patients and inform value-based healthcare initiatives. However, respondent burden needs to be carefully considered and addressed to avoid high rates of missing data and poor reporting of PRO results, which may lead to poor quality data for regulatory decision making and/or clinical care.",,doi:https://doi.org/10.1038/s41467-022-33826-4; html:https://europepmc.org/articles/PMC9556436; pdf:https://europepmc.org/articles/PMC9556436?pdf=render 32065794,https://doi.org/10.3233/jad-191163,Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer's Disease.,"Patel H, Iniesta R, Stahl D, Dobson RJB, Newhouse SJ.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,Y,Human; Biomarkers; Alzheimer’s disease; Dementia; Gene Expression; Neurodegenerative Disorders; Machine Learning; Microarray Analysis; Age-related Memory Disorders,,,"

Background

The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer's disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific.

Objective

Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature.

Methods

Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with 6,318 upsampled mixed controls consisting of Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls.

Results

The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7-64.6), 41.9% specificity (95% CI = 26.8-54.3), 13.6% PPV (95% CI = 9.9-18.5), and 81.1% NPV (95% CI = 73.3-87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5-52.0), 95.3% specificity (95% CI = 93.3-97.1), 61.4% PPV (95% CI = 53.8-69.6), and 89.7% NPV (95% CI = 87.8-91.4).

Conclusions

This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required.",,doi:https://doi.org/10.3233/JAD-191163; html:https://europepmc.org/articles/PMC7175937; pdf:https://europepmc.org/articles/PMC7175937?pdf=render 34639581,https://doi.org/10.3390/ijerph181910265,Identifying Prenatal and Postnatal Determinants of Infant Growth: A Structural Equation Modelling Based Cohort Analysis. ,"Morgan K, Zhou SM, Hill R, Lyons RA, Paranjothy S, Brophy ST.",,International journal of environmental research and public health,2021,2021-09-29,Y,,,,"The growth and maturation of infants reflect their overall health and nutritional status. The purpose of this study is to examine the associations of prenatal and early postnatal factors with infant growth (IG). A data-driven model was constructed by structural equation modelling to examine the relationships between pre- and early postnatal environmental factors and IG at age 12 months. The IG was a latent variable created from infant weight and waist circumference. Data were obtained on 274 mother-child pairs during pregnancy and the postnatal periods. Maternal pre-pregnancy BMI emerged as an important predictor of IG with both direct and indirect (mediated through infant birth weight) effects. Infants who gained more weight from birth to 6 months and consumed starchy foods daily at age 12 months, were more likely to be larger by age 12 months. Infant physical activity (PA) levels also emerged as a determinant. The constructed model provided a reasonable fit (χ2 (11) = 21.5, p < 0.05; RMSEA = 0.07; CFI = 0.94; SRMR = 0.05) to the data with significant pathways for all examined variables. Promoting healthy weight amongst women of child bearing age is important in preventing childhood obesity, and increasing daily infant PA is as important as a healthy infant diet.",,doi:https://doi.org/10.3390/ijerph181910265; html:https://europepmc.org/articles/PMC8507693; pdf:https://europepmc.org/articles/PMC8507693?pdf=render -34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674 30532623,https://doi.org/10.3897/bdj.6.e29232,"Modifier Ontologies for frequency, certainty, degree, and coverage phenotype modifier.","Endara L, Thessen AE, Cole HA, Walls R, Gkoutos G, Cao Y, Chong SS, Cui H.",,Biodiversity data journal,2018,2018-11-28,Y,Phenotype Modifiers; Modifier Ontology; Certainty Modifiers; Coverage Modifiers; Degree Modifiers; Frequency Modifiers; Literary Warrant; User Consensus; User Warrant,The Human Phenome,,"Background: When phenotypic characters are described in the literature, they may be constrained or clarified with additional information such as the location or degree of expression, these terms are called ""modifiers"". With effort underway to convert narrative character descriptions to computable data, ontologies for such modifiers are needed. Such ontologies can also be used to guide term usage in future publications. Spatial and method modifiers are the subjects of ontologies that already have been developed or are under development. In this work, frequency (e.g., rarely, usually), certainty (e.g., probably, definitely), degree (e.g., slightly, extremely), and coverage modifiers (e.g., sparsely, entirely) are collected, reviewed, and used to create two modifier ontologies with different design considerations. The basic goal is to express the sequential relationships within a type of modifiers, for example, usually is more frequent than rarely, in order to allow data annotated with ontology terms to be classified accordingly. Method: Two designs are proposed for the ontology, both using the list pattern: a closed ordered list (i.e., five-bin design) and an open ordered list design. The five-bin design puts the modifier terms into a set of 5 fixed bins with interval object properties, for example, one_level_more/less_frequently_than, where new terms can only be added as synonyms to existing classes. The open list approach starts with 5 bins, but supports the extensibility of the list via ordinal properties, for example, more/less_frequently_than, allowing new terms to be inserted as a new class anywhere in the list. The consequences of the different design decisions are discussed in the paper. CharaParser was used to extract modifiers from plant, ant, and other taxonomic descriptions. After a manual screening, 130 modifier words were selected as the candidate terms for the modifier ontologies. Four curators/experts (three biologists and one information scientist specialized in biosemantics) reviewed and categorized the terms into 20 bins using the Ontology Term Organizer (OTO) (http://biosemantics.arizona.edu/OTO). Inter-curator variations were reviewed and expressed in the final ontologies. Results: Frequency, certainty, degree, and coverage terms with complete agreement among all curators were used as class labels or exact synonyms. Terms with different interpretations were either excluded or included using ""broader synonym"" or ""not recommended"" annotation properties. These annotations explicitly allow for the user to be aware of the semantic ambiguity associated with the terms and whether they should be used with caution or avoided. Expert categorization results showed that 16 out of 20 bins contained terms with full agreements, suggesting differentiating the modifiers into 5 levels/bins balances the need to differentiate modifiers and the need for the ontology to reflect user consensus. Two ontologies, developed using the Protege ontology editor, are made available as OWL files and can be downloaded from https://github.com/biosemantics/ontologies. Contribution: We built the first two modifier ontologies following a consensus-based approach with terms commonly used in taxonomic literature. The five-bin ontology has been used in the Explorer of Taxon Concepts web toolkit to compute the similarity between characters extracted from literature to facilitate taxon concepts alignments. The two ontologies will also be used in an ontology-informed authoring tool for taxonomists to facilitate consistency in modifier term usage.",,doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render +34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674 35403174,https://doi.org/10.14218/jctp.2022.00003,Changing Trends in the Proportional Incidence and Five-year Net Survival of Screened and Non-screened Breast Cancers among Women During 1995-2011 in England.,"Wu H, Wong K, Lu SE, Broggio J, Zhang L.",,Journal of clinical and translational pathology,2022,2022-03-18,Y,Screening; Breast cancer; incidence; trends; Net Survival,,,"

Background and objectives

Uptake of breast cancer screening has been decreasing in England since 2007. However, the associated factors are unclear. On the other hand, survival among breast cancer patients have recently increased. We conducted a quasi-experimental analysis to test whether the trend-change in proportional incidence of non-screened cancers coincided with that in five-year net-survival.

Methods

We extracted population-based proportional incidence and age-standardized five-year net-survival data from Public Health England that included English women with invasive breast cancer diagnosed during 1995-2011 (linked to death certificates, followed through 2016). Piece-wise log-linear models with change-point/joinpoint were used to estimate temporal trends.

Results

Among 254,063 women in England with invasive breast cancer diagnosed during 1995-2011, there was downward-to-upward trend-change in proportional incidence of non-screened breast cancers (annual percent change [APC]=5.6 after 2007 versus APC=-3.5 before 2007, p<0.001) in diagnosis-year 2007, when a steeper upward-trend in age-standardized five-year net survival started (APC=5.7 after 2007/2008 versus APC=0.3 before 2007/2008, p<0.001). Net-survival difference of screened versus non-screened cancers also significantly narrowed (18% in 2007/2008 versus 5% in 2011). Similar associations were found in all strata of race, cancer stage, grade, and histology, except in Black patients or patients with stage I, stage III, or grade I cancer.

Conclusions

There was a downward-to-upward trend-change in proportional incidence of non-screened breast cancers in 2007 that coincided with a steeper upward-trend in age-standardized five-year net survival among English women in 2007. Survival benefits of breast cancer screening decreased during 2007-2011. The data support reduction of breast cancer screening in some patients, but future validation studies are warranted.",,doi:https://doi.org/10.14218/jctp.2022.00003; html:https://europepmc.org/articles/PMC8994161; pdf:https://europepmc.org/articles/PMC8994161?pdf=render 32182948,https://doi.org/10.3390/cells9030665,"Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases. ","Martin TC, Ilieva KM, Visconti A, Beaumont M, Kiddle SJ, Dobson RJB, Mangino M, Lim EM, Pezer M, Steves CJ, Bell JT, Wilson SG, Lauc G, Roederer M, Walsh JP, Spector TD, Karagiannis SN.",,Cells,2020,2020-03-09,Y,,Understanding the Causes of Disease,inflammatory and immune system,"The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.",,doi:https://doi.org/10.3390/cells9030665; html:https://europepmc.org/articles/PMC7140647; pdf:https://europepmc.org/articles/PMC7140647?pdf=render 35277454,https://doi.org/10.1136/heartjnl-2021-320417,Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.,"Gill S, Bunting KV, Sartini C, Cardoso VR, Ghoreishi N, Uh HW, Williams JA, Suzart-Woischnik K, Banerjee A, Asselbergs FW, Eijkemans M, Gkoutos GV, Kotecha D.",,Heart (British Cardiac Society),2022,2022-09-26,Y,Atrial fibrillation; Photoplethysmography; Smartphone,,,"

Objectives

Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.

Methods

This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.

Results

28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.

Conclusion

PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.",,doi:https://doi.org/10.1136/heartjnl-2021-320417; html:https://europepmc.org/articles/PMC9554073; pdf:https://europepmc.org/articles/PMC9554073?pdf=render @@ -980,22 +983,22 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 34974610,https://doi.org/10.1093/eurheartj/ehab874,The year in cardiovascular medicine 2021: digital health and innovation.,"Vardas PE, Asselbergs FW, van Smeden M, Friedman P.",,European heart journal,2022,2022-01-01,N,Cardiovascular Medicine; Machine Learning; Big Data; Digital Health; Ai-ecg; Ai-wearables,,,"This article presents some of the most important developments in the field of digital medicine that have appeared over the last 12 months and are related to cardiovascular medicine. The article consists of three main sections, as follows: (i) artificial intelligence-enabled cardiovascular diagnostic tools, techniques, and methodologies, (ii) big data and prognostic models for cardiovascular risk protection, and (iii) wearable devices in cardiovascular risk assessment, cardiovascular disease prevention, diagnosis, and management. To conclude the article, the authors present a brief further prospective on this new domain, highlighting existing gaps that are specifically related to artificial intelligence technologies, such as explainability, cost-effectiveness, and, of course, the importance of proper regulatory oversight for each clinical implementation.",,doi:https://doi.org/10.1093/eurheartj/ehab874 35537476,https://doi.org/10.1177/01410768221095245,Indirect effects of the pandemic: highlighting the need for data-driven policy and preparedness.,"Banerjee A, Sudlow C, Lawler M.",,Journal of the Royal Society of Medicine,2022,2022-05-10,Y,,,,,,doi:https://doi.org/10.1177/01410768221095245; html:https://europepmc.org/articles/PMC9234890; pdf:https://europepmc.org/articles/PMC9234890?pdf=render 31666244,https://doi.org/10.1136/archdischild-2019-317271,Behavioural difficulties in early childhood and risk of adolescent injury.,"Bandyopadhyay A, Tingay K, Akbari A, Griffiths L, Bedford H, Cortina-Borja M, Walton S, Dezateux C, Lyons RA, Brophy S.",,Archives of disease in childhood,2020,2019-10-30,Y,Hospital Admission; Routine Data; Strengths And Difficulties Questionnaire; A&e Attendance; Longitudinal Data Linkage,,,"

Objective

To evaluate long-term associations between early childhood hyperactivity and conduct problems (CP), measured using Strengths and Difficulties Questionnaire (SDQ) and risk of injury in early adolescence.

Design

Data linkage between a longitudinal birth cohort and routinely collected electronic health records.

Setting

Consenting Millennium Cohort Study (MCS) participants residing in Wales and Scotland.

Patients

3119 children who participated in the age 5 MCS interview.

Main outcome measures

Children with parent-reported SDQ scores were linked with hospital admission and Accident & Emergency (A&E) department records for injuries between ages 9 and 14 years. Negative binomial regression models adjusting for number of people in the household, lone parent, residential area, household poverty, maternal age and academic qualification, child sex, physical activity level and country of interview were fitted in the models.

Results

46% of children attended A&E or were admitted to hospital for injury, and 11% had high/abnormal scores for hyperactivity and CP. High/abnormal or borderline hyperactivity were not significantly associated with risk of injury, incidence rate ratio (IRR) with 95% CI of the high/abnormal and borderline were 0.92 (95% CI 0.74 to 1.14) and 1.16 (95% CI 0.88 to 1.52), respectively. Children with borderline CP had higher injury rates compared with those without CP (IRR 1.31, 95% CI 1.09 to 1.57).

Conclusions

Children with high/abnormal hyperactivity or CP scores were not at increased risk of injury; however, those with borderline CP had higher injury rates. Further research is needed to understand if those with difficulties receive treatment and support, which may reduce the likelihood of injuries.",,doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render -35038301,https://doi.org/10.2196/30523,Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.",,JMIR human factors,2022,2022-04-13,Y,Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Covid-19; Human-centered Design,,,"

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.",,doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380; pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF 31529485,https://doi.org/10.1111/bjd.18526,"The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.","Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Whitaker S, Watkins A, Langan SM, Hutchings HA, Lyons RA, Whitaker IS.",,The British journal of dermatology,2020,2019-12-01,Y,,Improving Public Health,,"

Background

Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce.

Objectives

To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival.

Methods

We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome.

Results

During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90).

Conclusions

Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.","This study investiages whether there is a smoking and socioeconomic status is linked to the risk of developing melanoma (a skin cancer). They used a Welsh database to find data on individuals who had melanoma and linked this data with smoking status and socioeconomic status on other national databases. They found that melanoma was less likely in those who smoked, but was associated with less chance of survival (due to health problems other than melanoma). Those in higher socioeconomic status had overall higher likelihood of survival.",doi:https://doi.org/10.1111/bjd.18526; html:https://europepmc.org/articles/PMC7383980; pdf:https://europepmc.org/articles/PMC7383980?pdf=render +35038301,https://doi.org/10.2196/30523,Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.",,JMIR human factors,2022,2022-04-13,Y,Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Covid-19; Human-centered Design,,,"

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.",,doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380; pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF 37269003,https://doi.org/10.1186/s13643-023-02261-x,Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.,"Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",,Systematic reviews,2023,2023-06-02,Y,Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19,,,"

Background

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.

Methods

Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.

Results

Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.

Discussion

Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.

Systematic review registration

PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render 37538142,https://doi.org/10.1093/ehjdh/ztad037,Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.,"Naderi H, Ramírez J, van Duijvenboden S, Pujadas ER, Aung N, Wang L, Anwar Ahmed Chahal C, Lekadir K, Petersen SE, Munroe PB.",,European heart journal. Digital health,2023,2023-06-01,Y,Electrocardiogram; Left ventricular hypertrophy; Cardiovascular Screening; Machine Learning; Cardiovascular Magnetic Resonance Imaging,,,"

Aims

Left ventricular hypertrophy (LVH) is an established, independent predictor of cardiovascular disease. Indices derived from the electrocardiogram (ECG) have been used to infer the presence of LVH with limited sensitivity. This study aimed to classify LVH defined by cardiovascular magnetic resonance (CMR) imaging using the 12-lead ECG for cost-effective patient stratification.

Methods and results

We extracted ECG biomarkers with a known physiological association with LVH from the 12-lead ECG of 37 534 participants in the UK Biobank imaging study. Classification models integrating ECG biomarkers and clinical variables were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% training and 20% test sets for performance evaluation. Ten-fold cross validation was applied with further validation testing performed by separating data based on UK Biobank imaging centres. QRS amplitude and blood pressure (P < 0.001) were the features most strongly associated with LVH. Classification with logistic regression had an accuracy of 81% [sensitivity 70%, specificity 81%, Area under the receiver operator curve (AUC) 0.86], SVM 81% accuracy (sensitivity 72%, specificity 81%, AUC 0.85) and RF 72% accuracy (sensitivity 74%, specificity 72%, AUC 0.83). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical variables alone. Validation testing by UK Biobank imaging centres demonstrated robustness of our models.

Conclusion

A combination of ECG biomarkers and clinical variables were able to predict LVH defined by CMR. Our findings provide support for the ECG as an inexpensive screening tool to risk stratify patients with LVH as a prelude to advanced imaging.",,doi:https://doi.org/10.1093/ehjdh/ztad037; html:https://europepmc.org/articles/PMC10393938; pdf:https://europepmc.org/articles/PMC10393938?pdf=render -37563721,https://doi.org/10.1186/s13063-023-07473-z,Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.,"McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.",,Trials,2023,2023-08-10,Y,Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge,,,"

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (""cluster"") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.",,doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render 36134690,https://doi.org/10.1242/dev.200654,Coupled myovascular expansion directs cardiac growth and regeneration.,"DeBenedittis P, Karpurapu A, Henry A, Thomas MC, McCord TJ, Brezitski K, Prasad A, Baker CE, Kobayashi Y, Shah SH, Kontos CD, Tata PR, Lumbers RT, Karra R.",,"Development (Cambridge, England)",2022,2022-09-22,N,Mouse; Cardiomyocyte proliferation; Heart regeneration; Myovascular,,,"Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled. We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth. Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.",,doi:https://doi.org/10.1242/dev.200654; pdf:https://journals.biologists.com/dev/article-pdf/149/18/dev200654/2167548/dev200654.pdf -36763324,https://doi.org/10.1007/s12687-023-00635-1,What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.,"Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.",,Journal of community genetics,2023,2023-02-10,N,,,,"The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.",,doi:https://doi.org/10.1007/s12687-023-00635-1; pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf +37563721,https://doi.org/10.1186/s13063-023-07473-z,Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.,"McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.",,Trials,2023,2023-08-10,Y,Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge,,,"

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (""cluster"") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.",,doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render 30659777,https://doi.org/10.1111/ijpo.12505,Are children with clinical obesity at increased risk of inpatient hospital admissions? An analysis using linked electronic health records in the UK millennium cohort study.,"Griffiths LJ, Cortina-Borja M, Bandyopadhyay A, Tingay K, De Stavola BL, Bedford H, Akbari A, Firman N, Lyons RA, Dezateux C.",,Pediatric obesity,2019,2019-01-18,Y,Obesity; Cohort study; Record Linkage; Health Service Utilization,Improving Public Health,,"

Background

Few studies have examined health service utilization of children with overweight or obesity by using linked electronic health records (EHRs).

Objective/methods

We analysed EHRs from 3269 children (1678 boys; 51.3% [weighted]) participating in the Millennium Cohort Study, living in Wales or Scotland at age seven whose parents consented to record linkage. We used height and weight measurements at age five to categorize children as obese (>98th centile) or overweight (>91st centile) (UK1990 clinical reference standards) and linked to hospital admissions, up to age 14 years, in the Patient Episode Database for Wales and Scottish Morbidity Records. Negative binomial regression models compared rates of inpatient admissions by weight status at age five.

Results

At age five, 11.5% and 6.7% of children were overweight or obese, respectively; 1221 (38%) children were subsequently admitted to hospital at least once. Admissions were not increased among children with overweight or obesity (adjusted rate ratio [RR], 95% confidence interval [CI]: 0.87, 0.68-1.10 and 1.16, 0.87-1.54, respectively).

Conclusions

In this nationally representative cohort of children in Wales and Scotland, those with overweight or obesity at entry to primary school did not have increased rates of hospital admissions in later childhood and early adolescence.",,doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render +36763324,https://doi.org/10.1007/s12687-023-00635-1,What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.,"Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.",,Journal of community genetics,2023,2023-02-10,N,,,,"The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.",,doi:https://doi.org/10.1007/s12687-023-00635-1; pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf 35595677,https://doi.org/10.1016/s2589-7500(22)00061-9,Identifying adverse childhood experiences with electronic health records of linked mothers and children in England: a multistage development and validation study.,"Syed S, Gonzalez-Izquierdo A, Allister J, Feder G, Li L, Gilbert R.",,The Lancet. Digital health,2022,2022-05-17,N,,,,"

Background

Electronic health records (EHRs) of mothers and children provide an opportunity to identify adverse childhood experiences (ACEs) during crucial periods of childhood development, yet well developed indicators of ACEs remain scarce. We aimed to develop clinically relevant indicators of ACEs for linked EHRs of mothers and children using a multistage prediction model of child maltreatment and maternal intimate partner violence (IPV).

Methods

In this multistage development and validation study, we developed a representative population-based birth cohort of mothers and children in England, followed from up to 2 years before birth to up to 5 years after birth across the Clinical Practice Research Datalink (CPRD) GOLD (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics mortality register. We included livebirths in England between July 1, 2004, and June 30, 2016, to mothers aged 16-55 years, who had registered with a general practitioner (GP) that met CPRD quality standards before 21 weeks of gestation. The primary outcome (reference standard) was any child maltreatment or maternal IPV in either the mother's or child's record from 2 years before birth (maternal IPV only) to 5 years after birth. We used seven prediction models, combined with expert ratings, to systematically develop indicators. We validated the final indicators by integrating results from machine learning models, survival analyses, and clustering analyses in the validation cohort.

Findings

We included data collected between July 1, 2002, and June 27, 2018. Of 376 006 eligible births, we included 211 393 mother-child pairs (422 786 patients) from 400 practices, of whom 126 837 mother-child pairs (60·0%; 240 practices) were randomly assigned to a derivation cohort and 84 556 pairs (40·0%; 160 practices) to a validation cohort. We included 63 indicators in six ACE domains: maternal mental health problems, maternal substance misuse, adverse family environments, child maltreatment, maternal IPV, and high-risk presentations of child maltreatment. Excluding the seven indicators in the reference standard, 56 indicators showed high discriminative validity for the reference standard of any child maltreatment or maternal IPV between 2 years before and 5 years after birth (validation cohort, area under the receiver operating characteristic curve 0·85 [95% CI 0·84-0·86]). During the 2 years before birth and 5 years after birth, the overall period prevalence of maternal IPV and child maltreatment (reference standard) was 2·3% (2876 of 126 837 pairs) in the derivation cohort and 2·3% (1916 of 84 556 pairs) in the validation cohort. During the 2 years before and after birth, the period prevalence was 39·1% (95% CI 38·7-39·5; 34 773 pairs) for any of the 63 ACE indicators, 22·2% (21·8-22·5%; 20 122 pairs) for maternal mental health problems, 15·7% (15·4-16·0%; 14 549 pairs) for adverse family environments, 8·1% (7·8-8·3%; 6808 pairs) for high-risk presentations of child maltreatment, 6·9% (6·7-7·2%; 7856 pairs) for maternal substance misuse, and 3·0% (2·9-3·2%; 2540 pairs) for any child maltreatment (2·4% [2·3-5·6%; 2051 pairs]) and maternal IPV (1·0% [0·8-1·0%; 875 pairs]). 62·6% (21 785 of 34 773 pairs) of ACEs were recorded in primary care only, and 72·3% (25 140 cases) were recorded in the maternal record only.

Interpretation

We developed clinically relevant indicators for identifying ACEs using the EHRs of mothers and children presenting to general practices and hospital admissions. Over 70% of ACEs were identified via maternal records and were recorded in primary care by GPs within 2 years of birth, reinforcing the importance of reviewing parental and carer records to inform clinical responses to children. ACE indicators can contribute to longitudinal surveillance informing public health policy and resource allocation. Further evaluation is required to determine how ACE indicators can be used in clinical practice.

Funding

None.",,doi:https://doi.org/10.1016/S2589-7500(22)00061-9 36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render 35210898,https://doi.org/10.2147/por.s353400,Deriving a Standardised Recommended Respiratory Disease Codelist Repository for Future Research.,"MacRae C, Whittaker H, Mukherjee M, Daines L, Morgan A, Iwundu C, Alsallakh M, Vasileiou E, O'Rourke E, Williams AT, Stone PW, Sheikh A, Quint JK.",,Pragmatic and observational research,2022,2022-02-16,Y,Asthma; COPD; Respiratory Tract Infections; Electronic Healthcare Records,,,"

Background

Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes.

Methods

We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided in article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature.

Results

Medline searches returned 1126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions.

Conclusion

Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made, greater consistency and transparency across studies using routine data to study respiratory diseases are needed.",,doi:https://doi.org/10.2147/POR.S353400; html:https://europepmc.org/articles/PMC8859726; pdf:https://europepmc.org/articles/PMC8859726?pdf=render 36403308,https://doi.org/10.1016/j.media.2022.102678,DragNet: Learning-based deformable registration for realistic cardiac MR sequence generation from a single frame.,"Zakeri A, Hokmabadi A, Bi N, Wijesinghe I, Nix MG, Petersen SE, Frangi AF, Taylor ZA, Gooya A.",,Medical image analysis,2023,2022-11-02,N,Uncertainty Estimation; Uk Biobank; Deep Learning; Deformable Temporal Image Registration; Sequential Image Data Generation; Variational Recurrent Neural Networks,,,"Deformable image registration (DIR) can be used to track cardiac motion. Conventional DIR algorithms aim to establish a dense and non-linear correspondence between independent pairs of images. They are, nevertheless, computationally intensive and do not consider temporal dependencies to regulate the estimated motion in a cardiac cycle. In this paper, leveraging deep learning methods, we formulate a novel hierarchical probabilistic model, termed DragNet, for fast and reliable spatio-temporal registration in cine cardiac magnetic resonance (CMR) images and for generating synthetic heart motion sequences. DragNet is a variational inference framework, which takes an image from the sequence in combination with the hidden states of a recurrent neural network (RNN) as inputs to an inference network per time step. As part of this framework, we condition the prior probability of the latent variables on the hidden states of the RNN utilised to capture temporal dependencies. We further condition the posterior of the motion field on a latent variable from hierarchy and features from the moving image. Subsequently, the RNN updates the hidden state variables based on the feature maps of the fixed image and the latent variables. Different from traditional methods, DragNet performs registration on unseen sequences in a forward pass, which significantly expedites the registration process. Besides, DragNet enables generating a large number of realistic synthetic image sequences given only one frame, where the corresponding deformations are also retrieved. The probabilistic framework allows for computing spatio-temporal uncertainties in the estimated motion fields. Our results show that DragNet performance is comparable with state-of-the-art methods in terms of registration accuracy, with the advantage of offering analytical pixel-wise motion uncertainty estimation across a cardiac cycle and being a motion generator. We will make our code publicly available.",,doi:https://doi.org/10.1016/j.media.2022.102678 35816976,https://doi.org/10.1016/j.jpsychires.2022.06.044,Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting.,"Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2022,2022-06-28,N,Atrial fibrillation; Warfarin; Serious Mental Illness; Oral Anticoagulation; Doacs,,,"

Objective

People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.

Methods

An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.

Results

Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019.

Conclusion

Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.",,doi:https://doi.org/10.1016/j.jpsychires.2022.06.044 37319288,https://doi.org/10.1371/journal.pone.0287264,Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity.,"Pikoula M, Kallis C, Madjiheurem S, Quint JK, Bafadhel M, Denaxas S.",,PloS one,2023,2023-06-15,Y,,,,"

Background

The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated.

Aims

Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease.

Methods

Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient.

Results

Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient.

Conclusions

Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline.",,doi:https://doi.org/10.1371/journal.pone.0287264; html:https://europepmc.org/articles/PMC10270623; pdf:https://europepmc.org/articles/PMC10270623?pdf=render -37101398,https://doi.org/10.1002/ejhf.2868,Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.,"Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.",,European journal of heart failure,2023,2023-05-18,N,Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence,,,"

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.",,doi:https://doi.org/10.1002/ejhf.2868 32249120,https://doi.org/10.1016/j.schres.2020.03.044,"Area deprivation, urbanicity, severe mental illness and social drift - A population-based linkage study using routinely collected primary and secondary care data.","Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, Owen MJ, O'Donovan M, John A.",,Schizophrenia research,2020,2020-04-02,N,Schizophrenia; Bipolar disorder; Deprivation; Severe Mental Illness; Urbanicity; Social Drift,Improving Public Health,mental health,"We investigated whether associations between area deprivation, urbanicity and elevated risk of severe mental illnesses (SMIs, including schizophrenia and bipolar disorder) is accounted for by social drift or social causation. We extracted primary and secondary care electronic health records from 2004 to 2015 from a population of 3.9 million. We identified prevalent and incident individuals with SMIs and their level of deprivation and urbanicity using the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator. The presence of social drift was determined by whether odds ratios (ORs) from logistic regression is greater than the incidence rate ratios (IRRs) from Poisson regression. Additionally, we performed longitudinal analysis to measure the proportion of change in deprivation level and rural/urban residence 10 years after an incident diagnosis of SMI and compared it to the general population using standardised rate ratios (SRRs). Prevalence and incidence of SMIs were significantly associated with deprivation and urbanicity (all ORs and IRRs significantly >1). ORs and IRRs were similar across all conditions and cohorts (ranging from 1.1 to 1.4). Results from the longitudinal analysis showed individuals with SMIs are more likely to move compared to the general population. However, they did not preferentially move to more deprived or urban areas. There was little evidence of downward social drift over a 10-year period. These findings have implications for the allocation of resources, service configuration and access to services in deprived communities, as well as, for broader public health interventions addressing poverty, and social and environmental contexts.",,doi:https://doi.org/10.1016/j.schres.2020.03.044 +37101398,https://doi.org/10.1002/ejhf.2868,Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.,"Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.",,European journal of heart failure,2023,2023-05-18,N,Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence,,,"

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.",,doi:https://doi.org/10.1002/ejhf.2868 36810251,https://doi.org/10.1172/jci.insight.156643,Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.,"Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",,JCI insight,2023,2023-02-22,Y,Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity,,,"Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",,doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render; doi:https://doi.org/10.12688/wellcomeopenres.15786.1 34459398,https://doi.org/10.3233/jad-210462,Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer's Disease.,"Handy A, Lord J, Green R, Xu J, Aarsland D, Velayudhan L, Hye A, Dobson R, Proitsi P, Alzheimer’s Disease Neuroimaging initiative, AddNeuroMed, and the GERAD1 Consortium.",,Journal of Alzheimer's disease : JAD,2021,2021-01-01,Y,Apolipoprotein E; Blood proteins; Alzheimer’s disease; C-reactive Protein; Apolipoprotein B-100; Insulin-like Growth Factor Binding Protein 2; Vitamin D-binding Protein; Mendelian Randomization Analysis; Polygenic Trait,,,"

Background

Blood plasma proteins have been associated with Alzheimer's disease (AD), but understanding which proteins are on the causal pathway remains challenging.

Objective

Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR).

Methods

Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/-PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR.

Results

For APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p < 0.00017). No protein APOE- PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p < 0.05) in either direction.

Conclusion

Apolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.",,doi:https://doi.org/10.3233/JAD-210462; html:https://europepmc.org/articles/PMC8609677; pdf:https://europepmc.org/articles/PMC8609677?pdf=render @@ -1010,12 +1013,12 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 34137744,https://doi.org/10.1097/ta.0000000000003317,Association between type 2 diabetes and long-term outcomes in middle-aged and older trauma patients.,"Daly SL, Gabbe BJ, Climie RE, Ekegren CL.",,The journal of trauma and acute care surgery,2022,2022-01-01,N,,,,"

Background

Diabetes is associated with increased hospital complications and mortality following trauma. However, there is limited research on the longer-term recovery of trauma patients with diabetes. The aim of this study was to explore the association between type 2 diabetes (T2D) and in-hospital and 24-month outcomes in major trauma patients.

Methods

In this cohort study using the Victorian State Trauma Registry, middle-aged and older adults (≥45 years) with major trauma were followed up at 24 months postinjury. Logistic regression (univariable and multivariable) analyses were used to determine the association between diabetes status and 24-month patient-reported outcomes. In-hospital outcomes were compared between groups using χ2 tests.

Results

Of the 11,490 participants who survived to hospital discharge, 8,493 survived to 24 months postinjury and were followed up at that time point: 953 people (11%) with and 7540 (89%) without T2D. People with T2D had a higher in-hospital death rate (19%) compared with people without T2D (16%; p < 0.001). After adjusting for confounders, people with T2D had poorer outcomes 24 months postinjury than people without T2D, with respect to functional recovery (Glasgow Outcome Scale Extended) (adjusted odds ratio [AOR], 0.58; 95% confidence interval [CI], 0.48-0.69) and return to work/study (AOR, 0.51; 95% CI, 0.37-0.71]). People with T2D experienced higher odds of problems with mobility (AOR, 1.92; 95% CI, 1.60-2.30), self-care (AOR, 1.94; 95% CI, 1.64, 2.29), usual activities (AOR, 1.50; 95% CI, 1.26-1.79), pain and discomfort (AOR, 1.75; 95% CI, 1.49-2.07), anxiety and depression (AOR, 1.45; 95% CI, 1.24, 1.70), and self-reported disability (AOR, 1.51; 95% CI, 1.28-1.79) than people without T2D.

Conclusion

Major trauma patients with T2D have a poorer prognosis than patients without T2D, both during their hospital admission and 24 months postinjury. Patients with T2D may need additional health care and support following trauma to reach their recovery potential.

Level of evidence

Prognostic, level III.",,doi:https://doi.org/10.1097/TA.0000000000003317 36691123,https://doi.org/10.1136/bmjopen-2022-063199,Feasibility of a new electronic patient-reported outcome (ePRO) system for an advanced therapy clinical trial in immune-mediated inflammatory disease (PROmics): protocol for a qualitative feasibility study.,"Hughes SE, McMullan C, Rowe A, Retzer A, Malpass R, Bathurst C, Davies EH, Frost C, McNamara G, Harding R, Price G, Wilson R, Walker A, Newsome PN, Calvert M.",,BMJ open,2022,2022-09-06,Y,information technology; immunology; Hepatology; Inflammatory Bowel Disease; Rheumatology,,,"

Introduction

The use of electronic patient-reported outcome (ePRO) systems to capture PRO data in clinical trials is increasing; however, their feasibility, acceptability and utility in clinical trials of advanced therapy medicinal products (ATMPs) are not yet well understood. This protocol describes a qualitative study that aims to evaluate the feasibility and acceptability of ePRO data capture using a trial-specific ePRO system (the PROmics system) within an advanced therapy trial involving patients with immune-mediated inflammatory disease (rheumatoid arthritis, lupus, primary sclerosing cholangitis (PSC) and Crohn's disease).

Methods and analysis

This protocol for a remote, qualitative, interview-based feasibility study is embedded within the POLARISE trial, a single-arm, phase II, multisite ATMP basket trial in the UK. 10-15 patients enrolled in the POLARISE trial and 10-15 research team members at the trial sites will be recruited. Participants will take part in semistructured interviews which will be transcribed verbatim and analysed thematically according to the framework method. Data collection and analysis will occur concurrently and iteratively. Researcher triangulation will be used to achieve a consensus-based analysis, enhancing rigour and trustworthiness.

Ethics and dissemination

This study was approved by the London-West London and GTAC Research Ethics Committee (Ref: 21/LO/0475). Informed consent will be obtained from all participants prior to data collection. The study findings will be published in peer-review journals and disseminated via conference presentations and other media. Our patient and public involvement and engagement group and ATMP stakeholder networks will be consulted to maximise dissemination and impact.

Trial registration number

ISRCTN80103507.",,doi:https://doi.org/10.1136/bmjopen-2022-063199; html:https://europepmc.org/articles/PMC9453996; pdf:https://europepmc.org/articles/PMC9453996?pdf=render 35025917,https://doi.org/10.1371/journal.pone.0261142,Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.,"Bechman K, Yates M, Mann K, Nagra D, Smith LJ, Rutherford AI, Patel A, Periselneris J, Walder D, Dobson RJB, Kraljevic Z, Teo JHT, Bernal W, Barker R, Galloway JB, Norton S.",,PloS one,2022,2022-01-13,Y,,,,"

Background

The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves.

Methods

The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.

Results

There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87].

Conclusion

There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.",,doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable -36729586,https://doi.org/10.2196/42965,Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.,"Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",,JMIR research protocols,2023,2023-02-02,Y,Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot,,,"

Background

Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.

Objective

The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.

Methods

We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.

Results

This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.

Conclusions

This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.

International registered report identifier (irrid)

PRR1-10.2196/42965.",,doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366 33342219,https://doi.org/10.1161/circoutcomes.120.007085,Estimating the Effect of Reduced Attendance at Emergency Departments for Suspected Cardiac Conditions on Cardiac Mortality During the COVID-19 Pandemic.,"Katsoulis M, Gomes M, Lai AG, Henry A, Denaxas S, Lagiou P, Nafilyan V, Humberstone B, Banerjee A, Hemingway H, Lumbers RT.",,Circulation. Cardiovascular quality and outcomes,2021,2020-12-20,Y,"Cardiovascular diseases; Coronavirus; Pandemic; Heart Disease; Death, Sudden, Cardiac",,,,,doi:https://doi.org/10.1161/CIRCOUTCOMES.120.007085; html:https://europepmc.org/articles/PMC7819531; pdf:https://europepmc.org/articles/PMC7819531?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCOUTCOMES.120.007085 35684987,https://doi.org/10.1111/camh.12571,Assessing the feasibility of a web-based outcome measurement system in child and adolescent mental health services - myHealthE a randomised controlled feasibility pilot study.,"Morris AC, Ibrahim Z, Heslin M, Moghraby OS, Stringaris A, Grant IM, Zalewski L, Pritchard M, Stewart R, Hotopf M, Pickles A, Dobson RJB, Simonoff E, Downs J.",,Child and adolescent mental health,2023,2022-06-09,Y,Child And Adolescent Mental Health; Remote Monitoring; Acceptability; Patient-reported Outcome Measures,,,"

Background

Interest in internet-based patient reported outcome measure (PROM) collection is increasing. The NHS myHealthE (MHE) web-based monitoring system was developed to address the limitations of paper-based PROM completion. MHE provides a simple and secure way for families accessing Child and Adolescent Mental Health Services to report clinical information and track their child's progress. This study aimed to assess whether MHE improves the completion of the Strengths and Difficulties Questionnaire (SDQ) compared with paper collection. Secondary objectives were to explore caregiver satisfaction and application acceptability.

Methods

A 12-week single-blinded randomised controlled feasibility pilot trial of MHE was conducted with 196 families accessing neurodevelopmental services in south London to examine whether electronic questionnaires are completed more readily than paper-based questionnaires over a 3-month period. Follow up process evaluation phone calls with a subset (n = 8) of caregivers explored system satisfaction and usability.

Results

MHE group assignment was significantly associated with an increased probability of completing an SDQ-P in the study period (adjusted hazard ratio (HR) 12.1, 95% CI 4.7-31.0; p = <.001). Of those caregivers' who received the MHE invitation (n = 68) 69.1% completed an SDQ using the platform compared to 8.8% in the control group (n = 68). The system was well received by caregivers, who cited numerous benefits of using MHE, for example, real-time feedback and ease of completion.

Conclusions

MHE holds promise for improving PROM completion rates. Research is needed to refine MHE, evaluate large-scale MHE implementation, cost effectiveness and explore factors associated with differences in electronic questionnaire uptake.",,doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571 +36729586,https://doi.org/10.2196/42965,Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.,"Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",,JMIR research protocols,2023,2023-02-02,Y,Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot,,,"

Background

Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.

Objective

The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.

Methods

We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.

Results

This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.

Conclusions

This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.

International registered report identifier (irrid)

PRR1-10.2196/42965.",,doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366 34125897,https://doi.org/10.1093/nar/gkab449,DGLinker: flexible knowledge-graph prediction of disease-gene associations.,"Hu J, Lepore R, Dobson RJB, Al-Chalabi A, M Bean D, Iacoangeli A.",,Nucleic acids research,2021,2021-07-01,Y,,,,"As a result of the advent of high-throughput technologies, there has been rapid progress in our understanding of the genetics underlying biological processes. However, despite such advances, the genetic landscape of human diseases has only marginally been disclosed. Exploiting the present availability of large amounts of biological and phenotypic data, we can use our current understanding of disease genetics to train machine learning models to predict novel genetic factors associated with the disease. To this end, we developed DGLinker, a webserver for the prediction of novel candidate genes for human diseases given a set of known disease genes. DGLinker has a user-friendly interface that allows non-expert users to exploit biomedical information from a wide range of biological and phenotypic databases, and/or to upload their own data, to generate a knowledge-graph and use machine learning to predict new disease-associated genes. The webserver includes tools to explore and interpret the results and generates publication-ready figures. DGLinker is available at https://dglinker.rosalind.kcl.ac.uk. The webserver is free and open to all users without the need for registration.",,doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render -37190768,https://doi.org/10.1017/s2045796023000276,The mental health of all children in contact with social services: a population-wide record-linkage study in Northern Ireland.,"McKenna S, O'Reilly D, Maguire A.",,Epidemiology and psychiatric sciences,2023,2023-05-16,Y,Mental health; Data Linkage; Children’s Social Care,,,"

Aims

Children in contact with social services are at high risk for mental ill health, but it is not known what proportion of the child population has contact with social services or how risk varies within this group compared to unexposed peers. We aim to quantify the extent and nature of contact with social services within the child population in Northern Ireland (NI) and the association with mental ill health. We also examine which social care experiences identify those most at risk.

Methods

This is a population-based record-linkage study of 497,269 children (aged under 18 years) alive and resident in NI in 2015 using routinely collected health and social care data. Exposure was categorized as (1) no contact, (2) referred but assessed as not in need (NIN), (3) child in need (CIN) and (4) child in care (CIC). Multilevel logistic regression analyses estimated odds ratios (ORs) for mental ill health indicated by receipt of psychotropic medication (antidepressants, anxiolytics, antipsychotics and hypnotics), psychiatric hospital admission and hospital-presenting self-harm or ideation.

Results

Over one in six children (17.2%, n = 85,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, n = 23,975) had contact in 2015. Likelihood of any mental ill health outcome increased incrementally with the level of contact with social services relative to unexposed peers: NIN (OR 5.90 [95% confidence interval (CI) 5.10-6.83]), CIN (OR 5.99 [95% CI 5.50-6.53]) and CIC (OR 12.60 [95% CI 10.63-14.95]). All tiers of contact, number of referrals, number of care episodes and placement type were strongly associated with the likelihood of mental ill health.

Conclusion

Children who have contact with social services account for a large and disproportionate amount of mental ill health in the child population. Likelihood of poor mental health across indicators is highest in care experienced children but also extends to the much larger population of children in contact with social services but never in care. Findings suggest a need for targeted mental health screening and enhanced support for all children in contact with social services.",,doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render 32975552,https://doi.org/10.1001/jamapediatrics.2020.4573,Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.,"Viner RM, Mytton OT, Bonell C, Melendez-Torres GJ, Ward J, Hudson L, Waddington C, Thomas J, Russell S, van der Klis F, Koirala A, Ladhani S, Panovska-Griffiths J, Davies NG, Booy R, Eggo RM.",,JAMA pediatrics,2021,2021-02-01,N,,,,"

Importance

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

Objective

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

Data sources

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

Study selection

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

Data extraction and synthesis

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

Main outcomes and measures

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

Results

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

Conclusions and relevance

In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.",,doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573 +37190768,https://doi.org/10.1017/s2045796023000276,The mental health of all children in contact with social services: a population-wide record-linkage study in Northern Ireland.,"McKenna S, O'Reilly D, Maguire A.",,Epidemiology and psychiatric sciences,2023,2023-05-16,Y,Mental health; Data Linkage; Children’s Social Care,,,"

Aims

Children in contact with social services are at high risk for mental ill health, but it is not known what proportion of the child population has contact with social services or how risk varies within this group compared to unexposed peers. We aim to quantify the extent and nature of contact with social services within the child population in Northern Ireland (NI) and the association with mental ill health. We also examine which social care experiences identify those most at risk.

Methods

This is a population-based record-linkage study of 497,269 children (aged under 18 years) alive and resident in NI in 2015 using routinely collected health and social care data. Exposure was categorized as (1) no contact, (2) referred but assessed as not in need (NIN), (3) child in need (CIN) and (4) child in care (CIC). Multilevel logistic regression analyses estimated odds ratios (ORs) for mental ill health indicated by receipt of psychotropic medication (antidepressants, anxiolytics, antipsychotics and hypnotics), psychiatric hospital admission and hospital-presenting self-harm or ideation.

Results

Over one in six children (17.2%, n = 85,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, n = 23,975) had contact in 2015. Likelihood of any mental ill health outcome increased incrementally with the level of contact with social services relative to unexposed peers: NIN (OR 5.90 [95% confidence interval (CI) 5.10-6.83]), CIN (OR 5.99 [95% CI 5.50-6.53]) and CIC (OR 12.60 [95% CI 10.63-14.95]). All tiers of contact, number of referrals, number of care episodes and placement type were strongly associated with the likelihood of mental ill health.

Conclusion

Children who have contact with social services account for a large and disproportionate amount of mental ill health in the child population. Likelihood of poor mental health across indicators is highest in care experienced children but also extends to the much larger population of children in contact with social services but never in care. Findings suggest a need for targeted mental health screening and enhanced support for all children in contact with social services.",,doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render 30729733,https://doi.org/10.1111/ijpo.12512,Predictors of objectively measured physical activity in 12-month-old infants: A study of linked birth cohort data with electronic health records.,"Raza H, Zhou SM, Todd C, Christian D, Marchant E, Morgan K, Khanom A, Hill R, Lyons RA, Brophy S.",,Pediatric obesity,2019,2019-02-06,Y,Gestation; Infants; postnatal development; Physical Activity,Improving Public Health,,"

Background

Physical activity (PA) levels are associated with long-term health, and levels of PA when young are predictive of adult activity levels.

Objectives

This study examines factors associated with PA levels in 12-month infants.

Method

One hundred forty-one mother-infant pairs were recruited via a longitudinal birth cohort study (April 2010 to March 2013). The PA level was collected using accelerometers and linked to postnatal notes and electronic medical records via the Secure Anonymised Information Linkage databank. Univariable and multivariable linear regressions were used to examine the factors associated with PA levels.

Results

Using univariable analysis, higher PA was associated with the following (P value less than 0.05): being male, larger infant size, healthy maternal blood pressure levels, full-term gestation period, higher consumption of vegetables (infant), lower consumption of juice (infant), low consumption of adult crisps (infant), longer breastfeeding duration, and more movement during sleep (infant) but fewer night wakings. Combined into a multivariable regression model (R2  = 0.654), all factors remained significant, showing lower PA levels were associated with female gender, smaller infant, preterm birth, higher maternal blood pressure, low vegetable consumption, high crisp consumption, and less night movement.

Conclusion

The PA levels of infants were strongly associated with both gestational and postnatal environmental factors. Healthy behaviours appear to cluster, and a healthy diet was associated with a more active infant. Boys were substantially more active than girls, even at age 12 months. These findings can help inform interventions to promote healthier lives for infants and to understand the determinants of their PA levels.",,doi:https://doi.org/10.1111/ijpo.12512; html:https://europepmc.org/articles/PMC6563068; pdf:https://europepmc.org/articles/PMC6563068?pdf=render 32979970,https://doi.org/10.1016/s0140-6736(20)31966-8,Models for mortality require tailoring in the context of the COVID-19 pandemic - Authors' reply.,"Banerjee A, Pasea L, Denaxas S, Williams B, Hemingway H.",,"Lancet (London, England)",2020,2020-09-01,Y,,,,,,doi:https://doi.org/10.1016/S0140-6736(20)31966-8; html:https://europepmc.org/articles/PMC7515579; pdf:https://europepmc.org/articles/PMC7515579?pdf=render 35699189,https://doi.org/10.1161/jaha.121.024248,Low-Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific.,"Cupido AJ, Asselbergs FW, Schmidt AF, Hovingh GK.",,Journal of the American Heart Association,2022,2022-06-14,Y,Genetics; Cardiovascular disease; Risk factor; Sex‐differences,,,"Background Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex-specific differential effect of genetically increased low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) and other lipid-associated diseases. Methods and Results This is a 2-sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80-variant LDL-C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex-specific LDL-C effects on lipids, carotid-intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL-C effect on CVD events was sex specific: per SD genetically increased LDL-C, female participants had a higher LDL-C increase but an attenuated CVD risk increase compared with male participants (LDL-C: female participants 0.71 mmol/L, 95% CI, 0.70-0.72 and male participants 0.57 mmol/L, 95% CI, 0.56-0.59. P for interaction: 5.03×10-60; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24-1.40 and male participants: OR, 1.52; 95% CI, 1.46-1.58. P for interaction: 9.88×10-5). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL-C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL-C was also associated with an attenuated carotid-intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex-specific weighted genetic scores showed similar results. Conclusions We found that genetically increased LDL-C has a sex-specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL-C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL-C targeted therapies for CVD management than female patients and warranting investigations into the sex-specific relative contribution of risk factors for CVD.",,doi:https://doi.org/10.1161/JAHA.121.024248; html:https://europepmc.org/articles/PMC9238661; pdf:https://europepmc.org/articles/PMC9238661?pdf=render @@ -1023,8 +1026,8 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 36713101,https://doi.org/10.1093/ehjdh/ztab082,A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.,"Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",,European heart journal. Digital health,2021,2021-10-01,Y,Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm),,,"

Aims

Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.

Methods and results

All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.

Conclusion

The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",,doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render 33655501,https://doi.org/10.1111/bjd.19885,Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.,"Mulick AR, Mansfield KE, Silverwood RJ, Budu-Aggrey A, Roberts A, Custovic A, Pearce N, Irvine AD, Smeeth L, Abuabara K, Langan SM.",,The British journal of dermatology,2021,2021-05-09,N,,,,"

Background

Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity.

Objectives

To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.

Methods

We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results.

Results

There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other.

Conclusions

Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.",,doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885 33096553,https://doi.org/10.1093/ajcn/nqaa266,"Association between diet and periodontitis: a cross-sectional study of 10,000 NHANES participants.","Wright DM, McKenna G, Nugent A, Winning L, Linden GJ, Woodside JV.",,The American journal of clinical nutrition,2020,2020-12-01,N,Diet; Periodontitis; Nhanes; Robust Regression; Treelet Transformation,,,"

Background

Periodontitis is a major cause of tooth loss globally. Risk factors include age, smoking, and diabetes. Intake of specific nutrients has been associated with periodontitis risk but there has been little research into the influence of overall diet, potentially more relevant when formulating dietary recommendations.

Objectives

We aimed to investigate potential associations between diet and periodontitis using novel statistical techniques for dietary pattern analysis.

Methods

Two 24-h dietary recalls and periodontal examination data from the cross-sectional US NHANES, 2009-2014 (n = 10,010), were used. Dietary patterns were extracted using treelet transformation, a data-driven hierarchical clustering and dimension reduction technique. Associations between each pattern [treelet component (TC)] and extent of periodontitis [proportion of sites with clinical attachment loss (CAL) ≥ 3 mm] were estimated using robust logistic quantile regression, adjusting for age, sex, ethnicity, education level, smoking, BMI, and diabetes.

Results

Eight TCs explained 21% of the variation in diet, 1 of which (TC1) was associated with CAL extent. High TC1 scores represented a diet rich in salad, fruit, vegetables, poultry and seafood, and plain water or tea to drink. There was a substantial negative gradient in CAL extent from the lowest to the highest decile of TC1 (median proportion of sites with CAL ≥ 3 mm: decile 1 = 19.1%, decile 10 = 8.1%; OR, decile 10 compared with decile 1: 0.67; 95% CI: 0.46, 0.99).

Conclusions

Most dietary patterns identified were not associated with periodontitis extent. One pattern, however, rich in salad, fruit, and vegetables and with plain water or tea to drink, was associated with lower CAL extent. Treelet transformation may be a useful approach for calculating dietary patterns in nutrition research.",,doi:https://doi.org/10.1093/ajcn/nqaa266 -37072241,https://doi.org/10.1136/heartjnl-2022-321888,Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.,"Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, Walter FM, Manisty CH, Robson J, Mamas MA, Harvey NC, Neubauer S, Petersen SE.",,Heart (British Cardiac Society),2023,2023-06-14,Y,epidemiology; Magnetic Resonance Imaging,,,"

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",,doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render; pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf 30969971,https://doi.org/10.1371/journal.pone.0213435,Are active children and young people at increased risk of injuries resulting in hospital admission or accident and emergency department attendance? Analysis of linked cohort and electronic hospital records in Wales and Scotland.,"Griffiths LJ, Cortina-Borja M, Tingay K, Bandyopadhyay A, Akbari A, DeStavola BL, Bedford H, Lyons RA, Dezateux C.",,PloS one,2019,2019-04-10,Y,,Improving Public Health,,"

Introduction

Children and young people (CYP) are encouraged to increase time spent being physically active, especially in moderate and vigorous intensity pursuits. However, there is limited evidence on the prospective association of activity levels with injuries resulting in use of hospital services. We examined the relationship between objectively-measured physical activity (PA) and subsequent injuries resulting in hospital admissions or accident and emergency department (A&E) attendances, using linked electronic hospital records (EHR) from a nationally representative prospective cohort of CYP in Wales and Scotland.

Methods

We analysed accelerometer-based estimates of moderate to vigorous (MVPA) and vigorous PA (VPA) from 1,585 (777 [46%] boys) seven-year-old Millennium Cohort Study members, living in Wales or Scotland, whose parents consented to linkage of cohort records to EHRs up until their 14th birthday. Negative binomial regression models adjusted by potential individual, household and area-level confounders, were fitted to estimate associations between average daily minutes of MVPA, and VPA (in 10-minute increments), and number of injury-related hospital admissions and/or A&E attendances from age nine to 14 years.

Results

CYP spent a median of 59.5 and 18.1 minutes in MVPA and VPA/day respectively, with boys significantly more active than girls; 47.3% of children experienced at least one injury-related admission or A&E attendance during the study period. Rates of injury-related hospital admission and/or A&E attendance were positively associated with MVPA and VPA in boys but not in girls: respective adjusted incidence rate ratios (95% CI) for boys: 1.09 (1.01, 1.17) and 1.16 (1.00, 1.34), and for girls: 0.94 (0.86, 1.03) and 0.85 (0.69, 1.04).

Conclusion

Boys but not girls who engage in more intense PA at age seven years are at higher risk of injury-related hospital admission or A&E attendance when aged nine to 14 years than their less active peers. This may reflect gender differences in the type and associated risks of activities undertaken. EHRs can make a useful contribution to injury surveillance and prevention if routinely augmented with information on context and setting of the injuries sustained. Injury prevention initiatives should not discourage engagement in PA and outdoor play given their over-riding health and social benefits.",,doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render +37072241,https://doi.org/10.1136/heartjnl-2022-321888,Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.,"Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, Walter FM, Manisty CH, Robson J, Mamas MA, Harvey NC, Neubauer S, Petersen SE.",,Heart (British Cardiac Society),2023,2023-06-14,Y,epidemiology; Magnetic Resonance Imaging,,,"

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",,doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render; pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf 36929232,https://doi.org/10.1002/jmri.28675,Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.,"Salih AM, Pujadas ER, Campello VM, McCracken C, Harvey NC, Neubauer S, Lekadir K, Nichols TE, Petersen SE, Raisi-Estabragh Z.",,Journal of magnetic resonance imaging : JMRI,2023,2023-03-16,N,Aging; Cardiac Imaging; Cardiac Health; Radiomics,,,"

Background

Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.

Purpose

To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.

Study type

Cross-sectional.

Population

A total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4).

Field strength/sequence

A 1.5 T/balanced steady-state free precession.

Assessment

An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The ""age gap"" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n = 49).

Statistical test

Multiple testing correction with false discovery method (threshold = 5%).

Results

The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10-26 ). Poor mental health associated with large age gaps, for example, ""disinterested"" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = -1.52, P = 7.44 × 10-6 ).

Data conclusion

This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.

Evidence level

1.

Technical efficacy

Stage 1.",,doi:https://doi.org/10.1002/jmri.28675 33634927,https://doi.org/10.1111/ans.16649,Risk factors for surgical site infections following spinal column trauma in an Australian trauma hospital.,"Baroun-Agob L, Liew S, Gabbe B.",,ANZ journal of surgery,2021,2021-02-26,N,Spine; Trauma; Risk factor; Surgical Wound Infection; Orthopaedic Surgery,,,"

Background

There is limited, and often conflicting, data in the literature about the prevalence and risk factors for surgical site infections (SSI) in spine surgery patients, with the majority consisting of elective spine surgery cohorts. Furthermore, there is no reported Australian data regarding rates of SSI in a spinal trauma cohort. The aim of this study is to identify factors associated with SSI following spinal column trauma.

Methods

Adult (16+ years) patients that underwent surgery following emergency admission for spinal trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was confirmed from the electronic medical record. Patient and clinical factors were analysed by SSI status. Generalized Estimating Equations were used to model predictors of SSI, with a P-value <0.05 deemed significant.

Results

Data for 458 patients and 520 surgical wounds were collected. Twenty-six (5.7%) patients developed an SSI. Staphylococcus aureus was the most common microorganism with methicillin-sensitive S. aureus found in 46% of SSI cases. A posterior surgical approach and same site reoperation were predictors of SSI with adjusted odds ratios (95% confidence intervals) of 4.26 (1.22-14.80, P = 0.02) and 4.99 (1.10-22.58, P = 0.04), respectively.

Conclusions

A posterior surgical approach and same site reoperation increased the risk of SSI after spinal trauma. Further research into modifiable associations within these and other factors will help mitigate the risk of SSI and hence decrease the personal and financial costs of this potentially devastating complication.",,doi:https://doi.org/10.1111/ans.16649 30999919,https://doi.org/10.1186/s12911-019-0805-0,Identifying clinically important COPD sub-types using data-driven approaches in primary care population based electronic health records.,"Pikoula M, Quint JK, Nissen F, Hemingway H, Smeeth L, Denaxas S.",,BMC medical informatics and decision making,2019,2019-04-18,Y,Cluster analysis; Electronic Health Records; Copd Exacerbations; Copd Epidemiology,The Human Phenome,,"

Background

COPD is a highly heterogeneous disease composed of different phenotypes with different aetiological and prognostic profiles and current classification systems do not fully capture this heterogeneity. In this study we sought to discover, describe and validate COPD subtypes using cluster analysis on data derived from electronic health records.

Methods

We applied two unsupervised learning algorithms (k-means and hierarchical clustering) in 30,961 current and former smokers diagnosed with COPD, using linked national structured electronic health records in England available through the CALIBER resource. We used 15 clinical features, including risk factors and comorbidities and performed dimensionality reduction using multiple correspondence analysis. We compared the association between cluster membership and COPD exacerbations and respiratory and cardiovascular death with 10,736 deaths recorded over 146,466 person-years of follow-up. We also implemented and tested a process to assign unseen patients into clusters using a decision tree classifier.

Results

We identified and characterized five COPD patient clusters with distinct patient characteristics with respect to demographics, comorbidities, risk of death and exacerbations. The four subgroups were associated with 1) anxiety/depression; 2) severe airflow obstruction and frailty; 3) cardiovascular disease and diabetes and 4) obesity/atopy. A fifth cluster was associated with low prevalence of most comorbid conditions.

Conclusions

COPD patients can be sub-classified into groups with differing risk factors, comorbidities, and prognosis, based on data included in their primary care records. The identified clusters confirm findings of previous clustering studies and draw attention to anxiety and depression as important drivers of the disease in young, female patients.",,doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render @@ -1035,39 +1038,39 @@ PMC10461733,https://doi.org/,The impact of poor housing and indoor air quality o 33543581,https://doi.org/10.1111/ans.16578,Outcomes of surgical site infections following spinal column trauma.,"Baroun-Agob L, Liew S, Gabbe B.",,ANZ journal of surgery,2021,2021-02-05,N,Spine; Trauma; Surgical Wound Infection; Orthopaedic Surgery; Patient-reported Outcome Measures,,,"

Background

Surgical site infections (SSI) are an undesirable outcome of spinal surgery for both the patient and healthcare system. To date, few studies have investigated the impact of SSI on patient-reported and clinical outcomes. Sepsis and readmission are potential sequelae of SSI, with sepsis potentially being life threatening. This study aimed to assess the association between SSI and patient outcomes in a spinal trauma cohort.

Methods

Adult (16+ years) patients who underwent emergency spinal surgery due to trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was abstracted from the electronic medical record and outcomes were compared between patients with and without an SSI. Clinical outcomes were obtained from the medical record, and patient-reported outcomes at 6 and 12 months were obtained from the Victorian Orthopaedic Trauma Outcomes Registry. Chi-squared tests were used to compare patient outcomes between groups.

Results

Of the 458 included patients, 26 (5.7%) developed an SSI. Patient-reported outcomes at 6 and 12 months were not different between the groups. An SSI was associated with sepsis (χ2 1 = 24.20, P < 0.01), readmission (χ2 1 = 215.34, P < 0.01), revision surgery (χ2 1 = 171.21, P < 0.01) and removal of implants (χ2 1 = 4.31, P = 0.04) within 12 months of discharge.

Conclusion

These findings indicate that spine trauma SSIs are not associated with patient-reported outcomes and may not have lasting effects on patients. Larger studies are required to assess further follow-up and support our findings and possibly distinguish outcomes between superficial and deep SSI.",,doi:https://doi.org/10.1111/ans.16578 PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USING PRE-PANDEMIC RISK OF MORTALITY IN INDIVIDUALS WITH CHRONIC KIDNEY DISEASE,"Dashtban M, Mizani M, Gonazalez-Izquierdo A, Corbett R, Denaxas S, Quint J, Mamza J, Morris T, Hemingway H, Sudlow C, Banerjee A.",,Kidney international reports,2022,2022-02-01,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8855010; pdf:https://europepmc.org/articles/PMC8855010?pdf=render 35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render; pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf -37538742,https://doi.org/10.1098/rsos.221469,Bayesian inference of polymerase dynamics over the exclusion process.,"Cavallaro M, Wang Y, Hebenstreit D, Dutta R.",,Royal Society open science,2023,2023-08-02,Y,Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics,,,"Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.",,doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render 35487318,https://doi.org/10.1016/j.ijcard.2022.04.067,Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction (NIHR Health Informatics Collaborative: TROP-CABG study).,"Benedetto U, Sinha S, Mulla A, Glampson B, Davies J, Panoulas V, Gautama S, Papadimitriou D, Woods K, Elliott P, Hemingway H, Williams B, Asselbergs FW, Melikian N, Krasopoulos G, Sayeed R, Wendler O, Baig K, Chukwuemeka A, Angelini GD, Sterne JAC, Johnson T, Shah AM, Perera D, Patel RS, Kharbanda R, Channon KM, Mayet J, Kaura A.",,International journal of cardiology,2022,2022-04-27,N,Troponin; Myocardial infarction; Coronary Artery Bypass Grafting; Timing-to-surgery,,,"Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients.",,doi:https://doi.org/10.1016/j.ijcard.2022.04.067 +37538742,https://doi.org/10.1098/rsos.221469,Bayesian inference of polymerase dynamics over the exclusion process.,"Cavallaro M, Wang Y, Hebenstreit D, Dutta R.",,Royal Society open science,2023,2023-08-02,Y,Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics,,,"Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.",,doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render 36355406,https://doi.org/10.2196/40707,Effectiveness of a Web-Based Intervention to Prevent Anxiety in the Children of Parents With Anxiety: Protocol for a Randomized Controlled Trial.,"Dunn A, Alvarez J, Arbon A, Bremner S, Elsby-Pearson C, Emsley R, Jones C, Lawrence P, Lester KJ, Majdandžić M, Morson N, Perry N, Simner J, Thomson A, Cartwright-Hatton S.",,JMIR research protocols,2022,2022-11-10,Y,Child; Parent; Youth; Anxiety; Pediatric; Mental health; Randomized controlled trial; Parenting; Rct; Online; Mental Well-being; Online Intervention; Digital Intervention,,,"

Background

Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks.

Objective

This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms.

Methods

 This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors.

Results

Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022.

Conclusions

The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety.

Trial registration

ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933.

International registered report identifier (irrid)

DERR1-10.2196/40707.",,doi:https://doi.org/10.2196/40707; html:https://europepmc.org/articles/PMC9693706; pdf:https://jmir.org/api/download?alt_name=resprot_v11i11e40707_app2.pdf&filename=4e6914231a45b12439d1932b760a7c34.pdf 33517835,https://doi.org/10.1080/17457300.2021.1876736,Identify the key characteristics of pedestrian collisions through in-depth interviews: a pilot study.,"Perkins M, Casalaz S, Mitra B, Gabbe B, Brown J, Oxley J, Cameron P, Beck B.",,International journal of injury control and safety promotion,2021,2021-01-31,N,Behaviour; Public Health; Pedestrian,,,"This study aimed to assess the feasibility of recruiting injured pedestrians from the emergency department of a major trauma centre, using an in-depth interview shortly post collision. Convenience sampling was used to prospectively recruit injured pedestrians from the Alfred Hospital Emergency and Trauma Centre. Of the 102 injured pedestrians, 39 met eligibility criteria and of these, 30 (77%) consented and completed the questionnaire. Over half of the collisions occurred at an intersection (57%), and of these the most common pre-impact vehicle manoeuvre was a vehicle turning into the street the pedestrian was crossing. In-depth interview during the early post-crash period was a feasible and effective method of collecting detailed data in an accessible sample. However, only 38% of patients met eligibility criteria. To enhance representativeness, supplementing interview data with police-reported crash data, recruiting from hospital wards and crash location assessment is recommended.",,doi:https://doi.org/10.1080/17457300.2021.1876736 35869974,https://doi.org/10.1093/ndt/gfac224,Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.,"Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,Y,Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes,,,"

Background

No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.

Methods

This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.

Results

There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age.

Conclusions

Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",,doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render; pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf 37612010,https://doi.org/10.1016/j.jacc.2023.05.065,Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.,"Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie ØH, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",,Journal of the American College of Cardiology,2023,2023-08-01,N,Early Detection; Arvc; Family Screening; Arrhythmogenic Cardiomyopathy; Deformation Imaging; Digital Twin,,,"

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.

Objectives

The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.

Methods

We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.

Results

We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.

Conclusions

Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",,doi:https://doi.org/10.1016/j.jacc.2023.05.065 36285341,https://doi.org/10.1080/17434440.2022.2132147,Data-driven monitoring in patients on left ventricular assist device support.,"Numan L, Moazeni M, Oerlemans MIFJ, Aarts E, Van Der Kaaij NP, Asselbergs FW, Van Laake LW.",,Expert review of medical devices,2022,2022-09-01,N,Prediction; Circadian rhythm; Algorithms; Remote Monitoring; Left Ventricular Assist Device; Lvad,,,"

Introduction

Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed.

Areas covered

The current review describes the principles of LVADs, the possibilities of (tele)monitoring using noninvasive and invasive devices. Furthermore, possibilities, challenges, and future perspectives in this emerging field are discussed.

Expert opinion

Several studies described initial experiences on telemonitoring in LVAD patients, using mobile phone applications to collect clinical data and pump data. This may replace frequent hospital visits in near future. In addition, algorithms were developed aiming to early detect pump thrombosis or driveline infections. Since not all complications are reflected by pump parameters, data from different sources should be combined to detect a broader spectrum of complications in an early stage. We need to focus on the development of sophisticated but understandable algorithms and infrastructure combining different data sources, while addressing essential aspects such as data safety, privacy, and cost-effectiveness.",,doi:https://doi.org/10.1080/17434440.2022.2132147 -35022215,https://doi.org/10.1136/bmj-2021-067519,Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.,"Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.",,BMJ (Clinical research ed.),2022,2022-01-12,Y,,,,"

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.",,doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render 35440446,https://doi.org/10.1136/bmjopen-2021-052514,Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, COVID-19 Genomics UK (COG-UK) Consortium, Breuer J.",,BMJ open,2022,2022-04-19,Y,Molecular biology; Infection control; epidemiology; Covid-19,,,"

Objectives

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

Design

Multicentre, prospective, interventional, superiority study.

Setting

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

Participants

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

Intervention

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

Primary and secondary outcome measures

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

Trial registration number

ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021.",,doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render +35022215,https://doi.org/10.1136/bmj-2021-067519,Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.,"Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.",,BMJ (Clinical research ed.),2022,2022-01-12,Y,,,,"

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.",,doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render 33766511,https://doi.org/10.1016/j.jid.2021.02.744,Raising the Bar for Randomized Trials Involving Artificial Intelligence: The SPIRIT-Artificial Intelligence and CONSORT-Artificial Intelligence Guidelines.,"Taylor M, Liu X, Denniston A, Esteva A, Ko J, Daneshjou R, Chan AW, SPIRIT-AI and CONSORT-AI Working Group.",,The Journal of investigative dermatology,2021,2021-03-22,N,,,,"Artificial intelligence (AI)-based applications have the potential to improve the quality and efficiency of patient care in dermatology. Unique challenges in the development and validation of these technologies may limit their generalizability and real-world applicability. Before the widespread adoption of AI interventions, randomized trials should be conducted to evaluate their efficacy, safety, and cost effectiveness in clinical settings. The recent Standard Protocol Items: Recommendations for Interventional Trials-AI extension and Consolidated Standards of Reporting Trials-AI extension guidelines provide recommendations for reporting the methods and results of trials involving AI interventions. High-quality trials will provide gold standard evidence to support the adoption of AI for the benefit of patient care.",,doi:https://doi.org/10.1016/j.jid.2021.02.744 34244270,https://doi.org/10.1136/bmjopen-2020-048008,Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.,"Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",,BMJ open,2021,2021-07-09,Y,epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine),,,"

Introduction

The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.

Methods and analysis

TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.

Ethics and dissemination

Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.

Prospero registration number

CRD42019140361 and CRD42019161764.",,doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render 35156082,https://doi.org/10.3389/fdgth.2022.833912,Artificial Intelligence and Statistics: Just the Old Wine in New Wineskins?,"Faes L, Sim DA, van Smeden M, Held U, Bossuyt PM, Bachmann LM.",,Frontiers in digital health,2022,2022-01-26,Y,Methodology; Statistics; Reporting Guideline; Machine Learning (Ml); Artificial Intelligence (Ai),,,,,doi:https://doi.org/10.3389/fdgth.2022.833912; html:https://europepmc.org/articles/PMC8825497; pdf:https://europepmc.org/articles/PMC8825497?pdf=render 32946613,https://doi.org/10.1111/cea.13741,Ethnicity-based differences in the incident risk of allergic diseases and autoimmune disorders: A UK-based retrospective cohort study of 4.4 million participants.,"Subramanian A, Adderley NJ, Gkoutos GV, Gokhale KM, Nirantharakumar K, Krishna MT.",,Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,2021,2020-09-29,N,Asthma; Rheumatoid; SLE; Autoimmunity; Rhinitis; Vitiligo; epidemiology; Ethnicity; Atopic Dermatitis,,,,,doi:https://doi.org/10.1111/cea.13741 35396183,https://doi.org/10.1016/s2589-7500(22)00003-6,The medical algorithmic audit.,"Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.",,The Lancet. Digital health,2022,2022-04-05,N,,,,"Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.",,doi:https://doi.org/10.1016/S2589-7500(22)00003-6 33789468,https://doi.org/10.1302/0301-620x.103b4.bjj-2020-1647.r1,Outcomes of severe lower limb injury with Mangled Extremity Severity Score ≥ 7.,"Hoogervorst LA, Hart MJ, Simpson PM, Kimmel LA, Oppy A, Edwards ER, Gabbe BJ.",,The bone & joint journal,2021,2021-04-01,N,Injury; Lower limb; Return To Work; Salvage; Functional Outcomes; Mess; Gos-e; Eq-5d-3l; Surgical Amputation; 2-Year,,,"

Aims

Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of ≥ 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity).

Methods

Patients aged ≥ 16 years with a fractured femur or tibia and a MESS of ≥ 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury.

Results

In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work.

Conclusion

A small proportion of patients with severe lower limb injury (MESS ≥ 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: Bone Joint J 2021;103-B(4):769-774.",,doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1 -36243582,https://doi.org/10.1016/j.injury.2022.09.052,Older trauma patients with isolated chest injuries have low rates of complications.,"Ferrah N, Beck B, Ibrahim J, Gabbe B, McLellan MS, Cameron P.",,Injury,2022,2022-10-07,N,Geriatric; Complication; Pneumonia; Chest Trauma; Older; Trauma Centre,,,"

Introduction

The number of older adults hospitalised for injury is growing rapidly. The population-adjusted incidence of isolated thoracic injuries in older adults is also growing. While some older adults are at high risk of post-traumatic complications, not all older adults will need treatment in a major trauma service (MTS). The aim of this study was to characterise older patients with isolated chest injuries, determine the rates of post-traumatic complications, including respiratory failure and pneumonia, and the factors associated with the risk of developing these complications.

Patients and methods

This was a retrospective review of patients aged 65 years and over with isolated chest trauma, from January 2007 to June 2017, using data from the Victorian State Trauma Registry. Patient characteristics and rates of complications were compared between patients with 1. isolated rib fractures, and 2. complex chest injury. Multivariable logistic regression was used to identify predictors of respiratory failure, and pneumonia.

Results

The study population comprised 5401 patients aged 65 years or more, with isolated chest injuries. Two-thirds (65%) of all patients had isolated rib fractures, and 58% of patients (n = 3156) were directly admitted to a non-major trauma centre. Complications were uncommon, with 5.45% of all patients (n = 295) having pneumonia and 3.2% (n = 175) having respiratory failure. Factors associated with increased risk of pneumonia and respiratory failure included advancing age, smoking, chronic obstructive pulmonary disease, congestive heart failure, and more severe and complex chest injury. The adjusted odds of complications were lowest amongst patients not classified as major trauma and receiving definitive treatment in non-MTS.

Discussion

Our findings suggest that rates of complications in older patients with isolated chest trauma in this study were low, and that there is a large group of patients with isolated, uncomplicated rib fractures, who may not need to be treated in a major trauma centre. Further work should be undertaken to appropriately risk stratify and manage older adults with isolated chest trauma.",,doi:https://doi.org/10.1016/j.injury.2022.09.052 31194737,https://doi.org/10.1371/journal.pgen.1008164,Genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, Ferguson A, McIntosh AM, Bailey MES, Smith DJ.",,PLoS genetics,2019,2019-06-13,Y,,Understanding the Causes of Disease,,"Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.",,doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?pdf=render +36243582,https://doi.org/10.1016/j.injury.2022.09.052,Older trauma patients with isolated chest injuries have low rates of complications.,"Ferrah N, Beck B, Ibrahim J, Gabbe B, McLellan MS, Cameron P.",,Injury,2022,2022-10-07,N,Geriatric; Complication; Pneumonia; Chest Trauma; Older; Trauma Centre,,,"

Introduction

The number of older adults hospitalised for injury is growing rapidly. The population-adjusted incidence of isolated thoracic injuries in older adults is also growing. While some older adults are at high risk of post-traumatic complications, not all older adults will need treatment in a major trauma service (MTS). The aim of this study was to characterise older patients with isolated chest injuries, determine the rates of post-traumatic complications, including respiratory failure and pneumonia, and the factors associated with the risk of developing these complications.

Patients and methods

This was a retrospective review of patients aged 65 years and over with isolated chest trauma, from January 2007 to June 2017, using data from the Victorian State Trauma Registry. Patient characteristics and rates of complications were compared between patients with 1. isolated rib fractures, and 2. complex chest injury. Multivariable logistic regression was used to identify predictors of respiratory failure, and pneumonia.

Results

The study population comprised 5401 patients aged 65 years or more, with isolated chest injuries. Two-thirds (65%) of all patients had isolated rib fractures, and 58% of patients (n = 3156) were directly admitted to a non-major trauma centre. Complications were uncommon, with 5.45% of all patients (n = 295) having pneumonia and 3.2% (n = 175) having respiratory failure. Factors associated with increased risk of pneumonia and respiratory failure included advancing age, smoking, chronic obstructive pulmonary disease, congestive heart failure, and more severe and complex chest injury. The adjusted odds of complications were lowest amongst patients not classified as major trauma and receiving definitive treatment in non-MTS.

Discussion

Our findings suggest that rates of complications in older patients with isolated chest trauma in this study were low, and that there is a large group of patients with isolated, uncomplicated rib fractures, who may not need to be treated in a major trauma centre. Further work should be undertaken to appropriately risk stratify and manage older adults with isolated chest trauma.",,doi:https://doi.org/10.1016/j.injury.2022.09.052 36669843,https://doi.org/10.1136/bmjopen-2022-064364,Implementation of a quality improvement programme using the Active Patient Link call and recall system to improve timeliness and equity of childhood vaccinations: protocol for a mixed-methods evaluation.,"Marszalek M, Hawking MKD, Gutierrez A, Dostal I, Ahmed Z, Firman N, Robson J, Bedford H, Billington A, Moss N, Dezateux C.",,BMJ open,2023,2023-01-20,Y,immunology; Public Health; Preventive Medicine; Community Child Health; Quality In Health Care; Paediatric Infectious Disease & Immunisation,,,"

Introduction

Call and recall systems provide actionable intelligence to improve equity and timeliness of childhood vaccinations, which have been disrupted during the COVID-19 pandemic. We will evaluate the effectiveness, fidelity and sustainability of a data-enabled quality improvement programme delivered in primary care using an Active Patient Link Immunisation (APL-Imms) call and recall system to improve timeliness and equity of uptake in a multiethnic disadvantaged urban population. We will use qualitative methods to evaluate programme delivery, focusing on uptake and use, implementation barriers and service improvements for clinical and non-clinical primary care staff, its fidelity and sustainability.

Methods and analysis

This is a mixed-methods observational study in 284 general practices in north east London (NEL). The target population will be preschool-aged children eligible to receive diphtheria, tetanus and pertussis (DTaP) or measles, mumps and rubella (MMR) vaccinations and registered with an NEL general practice. The intervention comprises an in-practice call and recall tool, facilitation and training, and financial incentives. The quantitative evaluation will include interrupted time Series analyses and Slope Index of Inequality. The primary outcomes will be the proportion of children receiving at least one dose of a DTaP-containing or MMR vaccination defined, respectively, as administered between age 6 weeks and 6 months or between 12 and 18 months of age. The qualitative evaluation will involve a 'Think Aloud' method and semistructured interviews of stakeholders to assess impact, fidelity and sustainability of the APL-Imms tool, and fidelity of the implementation by facilitators.

Ethics and dissemination

The research team has been granted permission from data controllers in participating practices to use deidentified data for audit purposes. As findings will be specific to the local context, research ethics approval is not required. Results will be disseminated in a peer-reviewed journal and to stakeholders, including parents, health providers and commissioners.",,doi:https://doi.org/10.1136/bmjopen-2022-064364; html:https://europepmc.org/articles/PMC9872487; pdf:https://europepmc.org/articles/PMC9872487?pdf=render 32831176,https://doi.org/10.7554/elife.58699,The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship. ,"Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.",,eLife,2020,2020-08-24,Y,,,,"A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.",,doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render 36198485,https://doi.org/10.1136/jech-2021-217986,Characteristics of enrolment in an intensive home-visiting programme among eligible first-time adolescent mothers in England: a linked administrative data cohort study.,"Cavallaro FL, Gilbert R, Wijlaars LP, Kennedy E, Howarth E, Kendall S, van der Meulen J, Calin MA, Reed L, Harron K.",,Journal of epidemiology and community health,2022,2022-10-05,Y,Adolescent; Public Health; Child Health,,,"

Background

Intensive home visiting for adolescent mothers may help reduce health disparities. Given limited resources, such interventions need to be effectively targeted. We evaluated which mothers were enrolled in the Family Nurse Partnership (FNP), an intensive home-visiting service for first-time young mothers commissioned in >130 local authorities in England since 2007.

Methods

We created a population-based cohort of first-time mothers aged 13-19 years giving birth in English National Health Service hospitals between 1 April 2010 and 31 March 2017, using administrative hospital data linked with FNP programme, educational and social care data. Mothers living in a local authority with an active FNP site were eligible. We described variation in enrolment rates across sites, and identified maternal and FNP site characteristics associated with enrolment.

Results

Of 110 520 eligible mothers, 25 680 (23.2% (95% CI: 23.0% to 23.5%)) were enrolled. Enrolment rates varied substantially across 122 sites (range: 11%-68%), and areas with greater numbers of first-time adolescent mothers achieved lower enrolment rates. Mothers aged 13-15 years were most likely to be enrolled (52%). However, only 26% of adolescent mothers with markers of vulnerability (including living in the most deprived areas and ever having been looked after as a child) were enrolled.

Conclusion

A substantial proportion of first-time adolescent mothers with vulnerability markers were not enrolled in FNP. Variation in enrolment across sites indicates insufficient commissioning of places that is not proportional to level of need, with mothers in areas with large numbers of other adolescent mothers least likely to receive support.",,doi:https://doi.org/10.1136/jech-2021-217986; html:https://europepmc.org/articles/PMC9664100; pdf:https://europepmc.org/articles/PMC9664100?pdf=render 34868617,https://doi.org/10.1177/20552076211048654,Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic.,"Cushnan D, Berka R, Bertolli O, Williams P, Schofield D, Joshi I, Favaro A, Halling-Brown M, Imreh G, Jefferson E, Sebire NJ, Reilly G, Rodrigues JCL, Robinson G, Copley S, Malik R, Bloomfield C, Gleeson F, Crotty M, Denton E, Dickson J, Leeming G, Hardwick HE, Baillie K, Openshaw PJ, Semple MG, Rubin C, Howlett A, Rockall AG, Bhayat A, Fascia D, Sudlow C, NCCID Collaborative, Jacob J.",,Digital health,2021,2021-01-01,Y,Artificial intelligence; Medicine; Imaging; general; Radiology; Respiratory; Machine Learning; Coronavirus Sars-Cov-2 Disease,,,"The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency. The National COVID-19 Chest Imaging Database, led by NHSX, British Society of Thoracic Imaging, Royal Surrey NHS Foundation Trust and Faculty, is an example of such a national initiative. Here, we summarise the experiences and challenges of setting up the National COVID-19 Chest Imaging Database, and the implications for future ambitions of national data curation in medical imaging to advance the safe adoption of artificial intelligence in healthcare.",,doi:https://doi.org/10.1177/20552076211048654; html:https://europepmc.org/articles/PMC8637703; pdf:https://europepmc.org/articles/PMC8637703?pdf=render -36828608,https://doi.org/10.1016/s2589-7500(22)00249-7,The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).,"Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.",,doi:https://doi.org/10.1016/S2589-7500(22)00249-7 33130851,https://doi.org/10.1093/ije/dyaa216,High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease.,"Zuber V, Gill D, Ala-Korpela M, Langenberg C, Butterworth A, Bottolo L, Burgess S.",,International journal of epidemiology,2021,2021-07-01,Y,Lipoproteins; Apolipoprotein B; Metabolomics; blood lipids; coronary artery disease; Mendelian Randomization; Risk Factor Selection,,,"

Background

Genetic variants can be used to prioritize risk factors as potential therapeutic targets via Mendelian randomization (MR). An agnostic statistical framework using Bayesian model averaging (MR-BMA) can disentangle the causal role of correlated risk factors with shared genetic predictors. Here, our objective is to identify lipoprotein measures as mediators between lipid-associated genetic variants and coronary artery disease (CAD) for the purpose of detecting therapeutic targets for CAD.

Methods

As risk factors we consider 30 lipoprotein measures and metabolites derived from a high-throughput metabolomics study including 24 925 participants. We fit multivariable MR models of genetic associations with CAD estimated in 453 595 participants (including 113 937 cases) regressed on genetic associations with the risk factors. MR-BMA assigns to each combination of risk factors a model score quantifying how well the genetic associations with CAD are explained. Risk factors are ranked by their marginal score and selected using false-discovery rate (FDR) criteria. We perform supplementary and sensitivity analyses varying the dataset for genetic associations with CAD.

Results

In the main analysis, the top combination of risk factors ranked by the model score contains apolipoprotein B (ApoB) only. ApoB is also the highest ranked risk factor with respect to the marginal score (FDR <0.005). Additionally, ApoB is selected in all sensitivity analyses. No other measure of cholesterol or triglyceride is consistently selected otherwise.

Conclusions

Our agnostic genetic investigation prioritizes ApoB across all datasets considered, suggesting that ApoB, representing the total number of hepatic-derived lipoprotein particles, is the primary lipid determinant of CAD.",,doi:https://doi.org/10.1093/ije/dyaa216; html:https://europepmc.org/articles/PMC8271202; pdf:https://europepmc.org/articles/PMC8271202?pdf=render 32895316,https://doi.org/10.1136/thoraxjnl-2020-215566,We need a robust evidence base to unravel the relationship between sex hormones and asthma.,"Sheikh A, Mukherjee M.",,Thorax,2020,2020-09-07,N,Asthma,,,,,doi:https://doi.org/10.1136/thoraxjnl-2020-215566 -36929968,https://doi.org/10.1016/s0140-6736(22)02235-8,Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.,"Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,"Lancet (London, England)",2022,2022-11-24,Y,,,,"

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.",,doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render +36828608,https://doi.org/10.1016/s2589-7500(22)00249-7,The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).,"Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.",,doi:https://doi.org/10.1016/S2589-7500(22)00249-7 33382071,https://doi.org/10.1093/schbul/sbaa176,Corrigendum to: Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,,,Schizophrenia bulletin,2021,2021-03-01,N,,,,,,doi:https://doi.org/10.1093/schbul/sbaa176; html:https://europepmc.org/articles/PMC7965055; pdf:https://europepmc.org/articles/PMC7965055?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa176 +36929968,https://doi.org/10.1016/s0140-6736(22)02235-8,Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.,"Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,"Lancet (London, England)",2022,2022-11-24,Y,,,,"

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.",,doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render 36854461,https://doi.org/10.1136/bmj-2022-073149,Realistic expectations are key to realising the benefits of polygenic scores.,"Sud A, Horton RH, Hingorani AD, Tzoulaki I, Turnbull C, Houlston RS, Lucassen A.",,BMJ (Clinical research ed.),2023,2023-02-28,Y,,,,,,doi:https://doi.org/10.1136/bmj-2022-073149; html:https://europepmc.org/articles/PMC9973128 34751629,https://doi.org/10.1080/09638288.2021.1998671,Long-term health and mobility of older adults following traumatic injury: a qualitative longitudinal study.,"Reeder S, Ameratunga S, Ponsford J, Fitzgerald M, Lyons R, Nunn A, Ekegren C, Cameron P, Gabbe B.",,Disability and rehabilitation,2022,2021-11-09,N,Ageing; Recovery; Qualitative; Disability; Older Adult; Traumatic Injury,,,"

Purpose

The aim of this study was to explore older adults' experiences of and approaches to managing their long-term health and mobility after traumatic injury.

Methods

A longitudinal qualitative study was undertaken with older adults following traumatic injury in Victoria, Australia. Fifteen participants (≥65 years) were interviewed at three years post-injury (n = 15), and re-interviewed at four (n = 14) and five years (n = 12) post-injury. Using a framework approach, a longitudinal thematic analysis was performed.

Results

Older age at the time of injury was identified by participants as a key factor influencing their recovery. Many participants reported actively attempting to regain their strength and fitness in the first five years following injury. However, their age, injury impacts, other health conditions, and weight gain made it difficult to achieve recovery goals. Many older adults reported a decline in their physical function over time. While these experiences and persistent disability constrained or changed the quality of social relationships, community participation, and independence, several participants described adapting to their functional limitations, and managing their secondary conditions over time.

Conclusion

In our cohort, the intertwined combination of ageing, injury, and comorbid conditions negatively affected health and mobility, reinforcing the need for preventative strategies.Implications for rehabilitationOlder adults recovering from traumatic injury may benefit from specialised care pathways that offer long-term and tailored therapies, with programs and services specific to their needs and goals.An integrated service approach by injury insurers, health care, primary care, disability, and aged care could more clearly identify and effectively address the individual needs and goals of older adults with complex conditions.Health and social services that work with people with injuries to develop personalised coping strategies can reduce anxiety related to uncertainty about the future, promote well-being, and support participation in valued activities.",,doi:https://doi.org/10.1080/09638288.2021.1998671 37419925,https://doi.org/10.1038/s41467-023-38930-7,Optimal strategies for learning multi-ancestry polygenic scores vary across traits.,"Lehmann B, Mackintosh M, McVean G, Holmes C.",,Nature communications,2023,2023-07-07,Y,,,,"Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.",,doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render 34261736,https://doi.org/10.1136/heartjnl-2021-319229,Heart failure medication dosage and survival in women and men seen at outpatient clinics.,"Bots SH, Onland-Moret NC, Tulevski II, van der Harst P, Cramer MJM, Asselbergs FW, Somsen GA, den Ruijter HM.",,Heart (British Cardiac Society),2021,2021-07-14,Y,epidemiology; Heart Failure; Electronic Health Records,,,"

Objective

Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care.

Methods

Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality.

Results

The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality.

Conclusion

Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF.",,doi:https://doi.org/10.1136/heartjnl-2021-319229; html:https://europepmc.org/articles/PMC8522453; pdf:https://europepmc.org/articles/PMC8522453?pdf=render 35452565,https://doi.org/10.1002/cpz1.373,The COPILOT Raw Illumina Genotyping QC Protocol.,"Patel H, Lee SH, Breen G, Menzel S, Ojewunmi O, Dobson RJB.",,Current protocols,2022,2022-04-01,N,Genotyping; Gwas; Illumina; Docker; Qc Pipeline,,,"The Illumina genotyping microarrays generate data in image format, which is processed by the platform-specific software GenomeStudio, followed by an array of complex bioinformatics analyses that rely on various software, different programming languages, and numerous dependencies to be installed and configured correctly. The entire process can be time-consuming, can lead to reproducibility errors, and can be a daunting task for bioinformaticians. To address this, we introduce the COPILOT protocol, which has been successfully used to transform raw Illumina genotype intensity data into high-quality analysis-ready data on tens of thousands of human patient samples that have been genotyped on a variety of Illumina genotyping arrays. This includes processing both mainstream and custom content genotyping chips with over 4 million markers per sample. The COPILOT QC protocol consists of two distinct tandem procedures to process raw Illumina genotyping data. The first protocol is an up-to-date process to systematically QC raw Illumina microarray genotyping data using the Illumina-specific GenomeStudio software. The second protocol takes the output from the first protocol and further processes the data through the COPILOT (Containerised wOrkflow for Processing ILlumina genOtyping daTa) containerized QC pipeline, to automate an array of complex bioinformatics analyses to improve data quality through a secondary clustering algorithm and to automatically identify typical Genome-Wide Association Study (GWAS) data issues, including gender discrepancies, heterozygosity outliers, related individuals, and population outliers, through ancestry estimation. The data is returned to the user in analysis-ready PLINK binary format and is accompanied by a comprehensive and interactive HTML summary report file which quickly helps the user understand the data and guides the user for further data analyses. The COPILOT protocol and containerized pipeline are also available at https://khp-informatics.github.io/COPILOT/index.html. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Processing raw Illumina genotyping data using GenomeStudio Basic Protocol 2: COPILOT: A containerised workflow for processing Illumina genotyping data.",,doi:https://doi.org/10.1002/cpz1.373 -34907415,https://doi.org/10.1093/ehjci/jeab266,Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.,"Raisi-Estabragh Z, McCracken C, Condurache D, Aung N, Vargas JD, Naderi H, Munroe PB, Neubauer S, Harvey NC, Petersen SE.",,European heart journal. Cardiovascular Imaging,2022,2022-08-01,Y,Mortality; Atrial fibrillation; Stroke; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Left ventricle; Vascular Risk Factors; Cardiovascular Outcomes; Lef; T Atrium,,,"

Aims

We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.

Methods and results

We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.

Conclusion

LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.",,doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render 32071531,https://doi.org/10.1016/j.jor.2020.02.001,Predictors of clavicle fixation in multiply injured patients.,"Tinney A, Moaveni AK, Kimmel LA, Gabbe BJ.",,Journal of orthopaedics,2020,2020-02-04,N,Trauma; Operative treatment; Trauma Registry; Clavicle Fracture; Surgical Fixation; Multiply Injured Patient,,,"

Introduction

Clavicle fractures account for approximately 10% of all fractures in multiply injured patients. Our study aims to determine factors associated with surgical fixation of the clavicle fracture in multiply injured patients.

Methods

Major adult trauma patients from 2005 to 2014 with a clavicle fracture were included. Multivariate analysis was undertaken to determine the variables associated with fixation.

Results

1779 patients (median age of 47 and a median Injury Severity Score of 17) were included. 273 (15%) patients underwent clavicle fixation. Factors associated with surgical fixation of the clavicle included: year, younger age, ICU admission, or an associated humerus or scapula fracture.",,doi:https://doi.org/10.1016/j.jor.2020.02.001; html:https://europepmc.org/articles/PMC7016330; pdf:https://europepmc.org/articles/PMC7016330?pdf=render; doi:https://doi.org/10.1016/j.jor.2020.02.001 +34907415,https://doi.org/10.1093/ehjci/jeab266,Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.,"Raisi-Estabragh Z, McCracken C, Condurache D, Aung N, Vargas JD, Naderi H, Munroe PB, Neubauer S, Harvey NC, Petersen SE.",,European heart journal. Cardiovascular Imaging,2022,2022-08-01,Y,Mortality; Atrial fibrillation; Stroke; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Left ventricle; Vascular Risk Factors; Cardiovascular Outcomes; Lef; T Atrium,,,"

Aims

We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.

Methods and results

We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.

Conclusion

LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.",,doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render 34000735,https://doi.org/10.1093/ije/dyab025,Commentary: Obstetric oxytocin exposure and risk of attention-deficit hyperactivity disorder and autism spectrum disorder in offspring-case closed.,"Morales DR, Nordeng HM.",,International journal of epidemiology,2021,2021-05-01,N,,,,,,doi:https://doi.org/10.1093/ije/dyab025 30181555,https://doi.org/10.1038/s41398-018-0236-1,"Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression.","Strawbridge RJ, Ward J, Lyall LM, Tunbridge EM, Cullen B, Graham N, Ferguson A, Johnston KJA, Lyall DM, Mackay D, Cavanagh J, Howard DM, Adams MJ, Deary I, Escott-Price V, O'Donovan M, McIntosh AM, Bailey MES, Pell JP, Harrison PJ, Smith DJ.",,Translational psychiatry,2018,2018-09-04,Y,,Understanding the Causes of Disease,,"Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects.",,doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?pdf=render 32321827,https://doi.org/10.1073/pnas.1912957117,Testing for dependence on tree structures.,"Behr M, Ansari MA, Munk A, Holmes C.",,Proceedings of the National Academy of Sciences of the United States of America,2020,2020-04-22,Y,Hypothesis Testing; Change-point Detection; Subgroup Detection; Tree Structures,,,"Tree structures, showing hierarchical relationships and the latent structures between samples, are ubiquitous in genomic and biomedical sciences. A common question in many studies is whether there is an association between a response variable measured on each sample and the latent group structure represented by some given tree. Currently, this is addressed on an ad hoc basis, usually requiring the user to decide on an appropriate number of clusters to prune out of the tree to be tested against the response variable. Here, we present a statistical method with statistical guarantees that tests for association between the response variable and a fixed tree structure across all levels of the tree hierarchy with high power while accounting for the overall false positive error rate. This enhances the robustness and reproducibility of such findings.",,doi:https://doi.org/10.1073/pnas.1912957117; html:https://europepmc.org/articles/PMC7211961; pdf:https://europepmc.org/articles/PMC7211961?pdf=render @@ -1086,9 +1089,9 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 33652931,https://doi.org/10.3390/jcm10050921,Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics. ,"Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.",,Journal of clinical medicine,2021,2021-02-26,Y,,,,"Dilated cardiomyopathy (DCM) is a leading cause of heart failure and life-threatening ventricular arrhythmias (LTVA). Work-up and risk stratification of DCM is clinically challenging, as there is great heterogeneity in phenotype and genotype. Throughout the last decade, improved genetic testing of patients has identified genotype-phenotype associations and enhanced evaluation of at-risk relatives leading to better patient prognosis. The field is now ripe to explore opportunities to improve personalised risk assessments. Multivariable risk models presented as ""risk calculators"" can incorporate a multitude of clinical variables and predict outcome (such as heart failure hospitalisations or LTVA). In addition, genetic risk scores derived from genome/exome-wide association studies can estimate an individual's lifetime genetic risk of developing DCM. The use of clinically granular investigations, such as late gadolinium enhancement on cardiac magnetic resonance imaging, is warranted in order to increase predictive performance. To this end, constructing big data infrastructures improves accessibility of data by using electronic health records, existing research databases, and disease registries. By applying methods such as machine and deep learning, we can model complex interactions, identify new phenotype clusters, and perform prognostic modelling. This review aims to provide an overview of the evolution of DCM definitions as well as its clinical work-up and considerations in the era of genomics. In addition, we present exciting examples in the field of big data infrastructures, personalised prognostic assessment, and artificial intelligence.",,doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render 36346654,https://doi.org/10.2196/38168,Developing an Automated Assessment of In-session Patient Activation for Psychological Therapy: Codevelopment Approach.,"Malins S, Figueredo G, Jilani T, Long Y, Andrews J, Rawsthorne M, Manolescu C, Clos J, Higton F, Waldram D, Hunt D, Perez Vallejos E, Moghaddam N.",,JMIR medical informatics,2022,2022-11-08,Y,Mental health; Machine Learning; Cognitive Behavioral Therapy; Natural Language Processing; Multimorbidity; Responsible Artificial Intelligence,,,"

Background

Patient activation is defined as a patient's confidence and perceived ability to manage their own health. Patient activation has been a consistent predictor of long-term health and care costs, particularly for people with multiple long-term health conditions. However, there is currently no means of measuring patient activation from what is said in health care consultations. This may be particularly important for psychological therapy because most current methods for evaluating therapy content cannot be used routinely due to time and cost restraints. Natural language processing (NLP) has been used increasingly to classify and evaluate the contents of psychological therapy. This aims to make the routine, systematic evaluation of psychological therapy contents more accessible in terms of time and cost restraints. However, comparatively little attention has been paid to algorithmic trust and interpretability, with few studies in the field involving end users or stakeholders in algorithm development.

Objective

This study applied a responsible design to use NLP in the development of an artificial intelligence model to automate the ratings assigned by a psychological therapy process measure: the consultation interactions coding scheme (CICS). The CICS assesses the level of patient activation observable from turn-by-turn psychological therapy interactions.

Methods

With consent, 128 sessions of remotely delivered cognitive behavioral therapy from 53 participants experiencing multiple physical and mental health problems were anonymously transcribed and rated by trained human CICS coders. Using participatory methodology, a multidisciplinary team proposed candidate language features that they thought would discriminate between high and low patient activation. The team included service-user researchers, psychological therapists, applied linguists, digital research experts, artificial intelligence ethics researchers, and NLP researchers. Identified language features were extracted from the transcripts alongside demographic features, and machine learning was applied using k-nearest neighbors and bagged trees algorithms to assess whether in-session patient activation and interaction types could be accurately classified.

Results

The k-nearest neighbors classifier obtained 73% accuracy (82% precision and 80% recall) in a test data set. The bagged trees classifier obtained 81% accuracy for test data (87% precision and 75% recall) in differentiating between interactions rated high in patient activation and those rated low or neutral.

Conclusions

Coproduced language features identified through a multidisciplinary collaboration can be used to discriminate among psychological therapy session contents based on patient activation among patients experiencing multiple long-term physical and mental health conditions.",,doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451 36798028,https://doi.org/10.1002/ehf2.14308,Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.,"Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.",,ESC heart failure,2023,2023-02-16,Y,Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump,,,"

Aims

Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.

Methods and results

We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P < 0.01) in 458 matched patients, with a median follow-up of 23 months. Within the matched cohort, HM3 patients had a median age of 58 years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59 years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P < 0.01). Pump thrombosis (P < 0.01) and ischaemic stroke (P < 0.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant.

Conclusions

HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.",,doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render -37348153,https://doi.org/10.1016/j.amjcard.2023.05.039,Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.,"Althunayyan A, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,The American journal of cardiology,2023,2023-06-20,N,,,,"The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.",,doi:https://doi.org/10.1016/j.amjcard.2023.05.039 -35748342,https://doi.org/10.1093/ije/dyac130,Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,International journal of epidemiology,2023,2023-02-01,Y,Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach,,,"

Background

Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.

Methods

We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.

Results

The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).

Conclusion

Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",,doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render 35242820,https://doi.org/10.3389/fcvm.2021.816985,A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms.,"Rauseo E, Omer M, Amir-Khalili A, Sojoudi A, Le TT, Cook SA, Hausenloy DJ, Ang B, Toh DF, Bryant J, Chin CWL, Paiva JM, Fung K, Cooper J, Khanji MY, Aung N, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2022-02-15,Y,Quality control; Assessment; Machine Learning; Cardiac Segmentation; Cardiac Magnetic Resonance (Cmr); Automated Contouring,,,"

Background

The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed.

Objective

We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm.

Methods

A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease.

Results

The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension.

Conclusions

Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.",,doi:https://doi.org/10.3389/fcvm.2021.816985; html:https://europepmc.org/articles/PMC8886212; pdf:https://europepmc.org/articles/PMC8886212?pdf=render +35748342,https://doi.org/10.1093/ije/dyac130,Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,International journal of epidemiology,2023,2023-02-01,Y,Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach,,,"

Background

Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.

Methods

We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.

Results

The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).

Conclusion

Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",,doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render +37348153,https://doi.org/10.1016/j.amjcard.2023.05.039,Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.,"Althunayyan A, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,The American journal of cardiology,2023,2023-06-20,N,,,,"The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.",,doi:https://doi.org/10.1016/j.amjcard.2023.05.039 35202588,https://doi.org/10.1016/s2213-8587(22)00015-8,Dose-response relationships for vitamin D and all-cause mortality - Authors' reply.,"Burgess S, Butterworth AS.",,The lancet. Diabetes & endocrinology,2022,2022-03-01,N,,,,,,doi:https://doi.org/10.1016/S2213-8587(22)00015-8 31529100,https://doi.org/10.1093/pm/pnz209,"Pain, Anxiety, and Depression in the First Two Years Following Transport-Related Major Trauma: A Population-Based, Prospective Registry Cohort Study.","Giummarra MJ, Simpson P, Gabbe BJ.",,"Pain medicine (Malden, Mass.)",2020,2020-02-01,N,Trauma; Injury; Prognostic; Recovery; Motor Vehicle,,,"

Objectives

This study aimed to characterize the population prevalence of pain and mental health problems postinjury and to identify risk factors that could improve service delivery to optimize recovery of at-risk patients.

Methods

This population-based registry cohort study included 5,350 adult survivors of transport-related major trauma injuries from the Victorian State Trauma Registry. Outcome profiles were generated separately for pain and mental health outcomes using the ""pain or discomfort"" and ""anxiety or depression"" items of the EuroQol Five Dimensions Three-Level questionnaire at six, 12, and 24 months postinjury. Profiles were ""resilient"" (no problems at every follow-up), ""recovered"" (problems at six- and/or 12-month follow-up that later resolved), ""worsening"" (problems at 12 and/or 24 months after no problems at six and/or 12 months), and ""persistent"" (problems at every follow-up).

Results

Most participants had persistent (pain/discomfort, N = 2,171, 39.7%; anxiety/depression, N = 1,428, 26.2%) and resilient profiles (pain/discomfort, N = 1,220, 22.3%; anxiety/depression, N = 2,055, 37.7%), followed by recovered (pain/discomfort, N = 1,116, 20.4%; anxiety/depression, N = 1,025, 18.8%) and worsening profiles (pain/discomfort, N = 956, 17.5%; anxiety/depression, N = 948, 17.4%). Adjusted multinomial logistic regressions showed increased risk of problems (persistent, worsening, or resolved) vs no problems (resilient) in relation to female sex, middle age, neighborhood disadvantage, pre-injury unemployment, pre-injury disability, and spinal cord injury. People living in rural areas, motorcyclists, pedal cyclists, and people with head, chest, and abdominal injuries had lower risk of problems.

Discussion

Targeted interventions delivered to people with the risk factors identified may help to attenuate the severity and impact of pain and mental health problems after transport injury.",,doi:https://doi.org/10.1093/pm/pnz209 34386668,https://doi.org/10.1016/j.ekir.2021.05.031,Impact of Using Risk-Based Stratification on Referral of Patients With Chronic Kidney Disease From Primary Care to Specialist Care in the United Kingdom.,"Bhachu HK, Cockwell P, Subramanian A, Adderley NJ, Gokhale K, Fenton A, Kyte D, Nirantharakumar K, Calvert M.",,Kidney international reports,2021,2021-06-01,Y,Cross-sectional study; Chronic Kidney Disease; Guidelines; Disease Progression; Patient Referral; Kidney Failure Risk Equation,,,"

Introduction

The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known.

Methods

A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines versus the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017.

Results

In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results.

Conclusions

A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified.",,doi:https://doi.org/10.1016/j.ekir.2021.05.031; html:https://europepmc.org/articles/PMC8343777; pdf:https://europepmc.org/articles/PMC8343777?pdf=render @@ -1102,8 +1105,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35477524,https://doi.org/10.1136/bmj-2022-070230,Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.,"Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",,BMJ (Clinical research ed.),2022,2022-04-27,Y,,,,"

Objective

To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).

Design

Multiphase, prospective mixed methods study.

Setting

Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.

Participants

13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.

Main outcome measures

Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.

Results

SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.

Conclusions

SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.",,doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?pdf=render 36576811,https://doi.org/10.1001/jamacardio.2022.4466,Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.,"Marston NA, Pirruccello JP, Melloni GEM, Koyama S, Kamanu FK, Weng LC, Roselli C, Kamatani Y, Komuro I, Aragam KG, Butterworth AS, Ito K, Lubitz SA, Ellinor PT, Sabatine MS, Ruff CT.",,JAMA cardiology,2023,2023-02-01,N,,,,"

Importance

The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective

To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, setting, and participants

This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.

Exposures

Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%).

Main outcomes and measures

Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).

Results

A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.

Conclusions and relevance

Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.",,doi:https://doi.org/10.1001/jamacardio.2022.4466 33180769,https://doi.org/10.1371/journal.pone.0240902,"Probable PTSD, depression and anxiety in 40,299 UK police officers and staff: Prevalence, risk factors and associations with blood pressure.","Stevelink SAM, Opie E, Pernet D, Gao H, Elliott P, Wessely S, Fear NT, Hotopf M, Greenberg N.",,PloS one,2020,2020-11-12,Y,,,,"

Introduction

Police employees undertake challenging duties which may adversely impact their health. This study explored the prevalence of and risk factors for probable mental disorders amongst a representative sample of UK police employees. The association between mental illness and alterations in blood pressure was also explored.

Methods

Data were used from the Airwave Health Monitoring Study which was established to monitor the possible physical health impacts of a new communication system on police employees. Data included sociodemographic characteristics, lifestyle habits, depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms and blood pressure. Descriptive statistics were used to explore the prevalence of probable mental disorders and associated factors. Stepwise linear regression was conducted, controlling for confounding variables, to examine associations between mental disorders and blood pressure.

Results

The sample included 40,299 police staff, police constable/sergeants and inspectors or above. Probable depression was most frequently reported (9.8%), followed by anxiety (8.5%) and PTSD (3.9%). Groups at risk for probable mental disorders included police staff, and police employees who reported drinking heavily. Police employees exposed to traumatic incidents in the past six months had a doubling in rates of anxiety or depression and a six-fold increase in PTSD compared to those with no recent trauma exposure. Adjusted logistic regression models did not reveal any significant association between probable mental disorders and systolic blood pressure but significantly elevated diastolic blood pressure (≈1mmHg) was found across mental disorders.

Conclusions

These results show lower rates of probable mental disorders, especially PTSD, than reported in other studies focusing on police employees. Although mental ill health was associated with increased diastolic blood pressure, this was unlikely to be clinically significant. These findings highlight the importance of continued health monitoring of members of the UK police forces, focusing on employees recently exposed to traumatic incidents, heavy drinkers and police staff.",,doi:https://doi.org/10.1371/journal.pone.0240902; html:https://europepmc.org/articles/PMC7660485; pdf:https://europepmc.org/articles/PMC7660485?pdf=render -32282926,https://doi.org/10.1111/bjd.19122,"Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark.","Wong AYS, Kjaersgaard A, Frøslev T, Forbes HJ, Mansfield KE, Silverwood RJ, Sørensen HT, Smeeth L, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-06-10,N,,,,,,doi:https://doi.org/10.1111/bjd.19122 30909231,https://doi.org/10.3233/jad-181085,A Meta-Analysis of Alzheimer's Disease Brain Transcriptomic Data.,"Patel H, Dobson RJB, Newhouse SJ.",,Journal of Alzheimer's disease : JAD,2019,2019-01-01,Y,Human; Meta-analysis; Neuropathology; Mental disorders; Alzheimer’s disease; Gene Expression; Neurodegenerative Disorders; Microarray Analysis,,,"

Background

Microarray technologies have identified imbalances in the expression of specific genes and biological pathways in Alzheimer's disease (AD) brains. However, there is a lack of reproducibility across individual AD studies, and many related neurodegenerative and mental health disorders exhibit similar perturbations.

Objective

Meta-analyze publicly available transcriptomic data from multiple brain-related disorders to identify robust transcriptomic changes specific to AD brains.

Methods

Twenty-two AD, eight schizophrenia, five bipolar disorder, four Huntington's disease, two major depressive disorder, and one Parkinson's disease dataset totaling 2,667 samples and mapping to four different brain regions (temporal lobe, frontal lobe, parietal lobe, and cerebellum) were analyzed. Differential expression analysis was performed independently in each dataset, followed by meta-analysis using a combining p-value method known as Adaptively Weighted with One-sided Correction.

Results

Meta-analysis identified 323, 435, 1,023, and 828 differentially expressed genes specific to the AD temporal lobe, frontal lobe, parietal lobe, and cerebellum brain regions, respectively. Seven of these genes were consistently perturbed across all AD brain regions with SPCS1 gene expression pattern replicating in RNA-Seq data. A further nineteen genes were perturbed specifically in AD brain regions affected by both plaques and tangles, suggesting possible involvement in AD neuropathology. In addition, biological pathways involved in the ""metabolism of proteins"" and viral components were significantly enriched across AD brains.

Conclusion

This study identified transcriptomic changes specific to AD brains, which could make a significant contribution toward the understanding of AD disease mechanisms and may also provide new therapeutic targets.",,doi:https://doi.org/10.3233/JAD-181085; html:https://europepmc.org/articles/PMC6484273; pdf:https://europepmc.org/articles/PMC6484273?pdf=render +32282926,https://doi.org/10.1111/bjd.19122,"Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark.","Wong AYS, Kjaersgaard A, Frøslev T, Forbes HJ, Mansfield KE, Silverwood RJ, Sørensen HT, Smeeth L, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-06-10,N,,,,,,doi:https://doi.org/10.1111/bjd.19122 36344532,https://doi.org/10.1038/s41598-022-21663-w,Atrial fibrillation prediction by combining ECG markers and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.",,Scientific reports,2022,2022-11-07,Y,,,,"Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p < 0.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p < 0.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.",,doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render 31827124,https://doi.org/10.1038/s41598-019-54849-w,Improving the odds of drug development success through human genomics: modelling study.,"Hingorani AD, Kuan V, Finan C, Kruger FA, Gaulton A, Chopade S, Sofat R, MacAllister RJ, Overington JP, Hemingway H, Denaxas S, Prieto D, Casas JP.",,Scientific reports,2019,2019-12-11,Y,,,,"Lack of efficacy in the intended disease indication is the major cause of clinical phase drug development failure. Explanations could include the poor external validity of pre-clinical (cell, tissue, and animal) models of human disease and the high false discovery rate (FDR) in preclinical science. FDR is related to the proportion of true relationships available for discovery (γ), and the type 1 (false-positive) and type 2 (false negative) error rates of the experiments designed to uncover them. We estimated the FDR in preclinical science, its effect on drug development success rates, and improvements expected from use of human genomics rather than preclinical studies as the primary source of evidence for drug target identification. Calculations were based on a sample space defined by all human diseases - the 'disease-ome' - represented as columns; and all protein coding genes - 'the protein-coding genome'- represented as rows, producing a matrix of unique gene- (or protein-) disease pairings. We parameterised the space based on 10,000 diseases, 20,000 protein-coding genes, 100 causal genes per disease and 4000 genes encoding druggable targets, examining the effect of varying the parameters and a range of underlying assumptions, on the inferences drawn. We estimated γ, defined mathematical relationships between preclinical FDR and drug development success rates, and estimated improvements in success rates based on human genomics (rather than orthodox preclinical studies). Around one in every 200 protein-disease pairings was estimated to be causal (γ = 0.005) giving an FDR in preclinical research of 92.6%, which likely makes a major contribution to the reported drug development failure rate of 96%. Observed success rate was only slightly greater than expected for a random pick from the sample space. Values for γ back-calculated from reported preclinical and clinical drug development success rates were also close to the a priori estimates. Substituting genome wide (or druggable genome wide) association studies for preclinical studies as the major information source for drug target identification was estimated to reverse the probability of late stage failure because of the more stringent type 1 error rate employed and the ability to interrogate every potential druggable target in the same experiment. Genetic studies conducted at much larger scale, with greater resolution of disease end-points, e.g. by connecting genomics and electronic health record data within healthcare systems has the potential to produce radical improvement in drug development success rate.","This study investigates the unreliability of target identification leading to low development sucess rates, inefficiency and escalating costs to healthcare users. The more targeted use of genomics couldimprove improved efficency.",doi:https://doi.org/10.1038/s41598-019-54849-w; html:https://europepmc.org/articles/PMC6906499; pdf:https://europepmc.org/articles/PMC6906499?pdf=render 35536740,https://doi.org/10.1136/bmjopen-2021-052884,Gaps in antihypertensive and statin treatments and benefits of optimisation: a modelling study in a 1 million ethnically diverse urban population in UK.,"Wu R, Rison SCG, Raisi-Estabragh Z, Dostal I, Carvalho C, Robson J, Mihaylova B.",,BMJ open,2021,2021-12-30,Y,Hypertension; Preventive Medicine; Ischaemic Heart Disease; Primary Care; Health Policy; Quality In Health Care,,,"

Objectives

To characterise gaps in antihypertensive treatment in people with hypertension and statin treatment in people with cardiovascular diseases (CVD) in a large urban population and quantify the health and economic impacts of their optimisation.

Design

A cross-sectional population study and a long-term CVD decision model.

Setting

Primary care, UK.

Participants

All adults with diagnosed hypertension or CVD in a population of about 1 million people, served by 123 primary care practices in London, UK in 2019.

Interventions

Following UK clinical guidelines, all adults with diagnosed hypertension were categorised into optimal, suboptimal and untreated groups with respect to their antihypertensive treatment, and all adults with diagnosed CVD were categorised in the same manner with respect to their statin treatment.

Outcomes

Proportion of patients suboptimally treated or untreated. Projected cardiovascular events avoided, years and quality-adjusted life years (QALYs) gained and healthcare costs saved with optimised treatments.

Results

21 954 of the 91 828 adults with hypertension (24%; mean age 59 years; 49% women) and 9062 of the 23 723 adults with CVD (38%; mean age 69 years; 43% women) were not optimally treated with antihypertensive or statin treatment, respectively. Per 1000 additional patients optimised over 5 years, hypertension treatment is projected to prevent 25 (95% CI 16 to 32) major vascular events (MVEs) and 7 (3 to 10) vascular deaths, statin treatment, 28 (22 to 33) MVEs and 6 (4 to 7) vascular deaths. Over their lifespan, a patient with uncontrolled hypertension aged 60-69 years is projected to gain 0.64 (95% CI 0.36 to 0.87) QALYs with optimised hypertension treatment, and a similarly aged patient with previous CVD not optimally treated with statin is projected to gain 0.3 (0.24 to 0.37) QALYs with optimised statin treatment. In both cases, the hospital cost savings minus extra medication costs were about £1100 per person over remaining lifespan.

Conclusions

Optimising cardiovascular treatments can cost-effectively reduce cardiovascular risk and improve life expectancy.",,doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render @@ -1115,39 +1118,39 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 34145643,https://doi.org/10.1111/jdv.17450,Describing the burden of the COVID-19 pandemic in people with psoriasis: findings from a global cross-sectional study.,"Mahil SK, Yates M, Yiu ZZN, Langan SM, Tsakok T, Dand N, Mason KJ, McAteer H, Meynell F, Coker B, Vincent A, Urmston D, Vesty A, Kelly J, Lancelot C, Moorhead L, Bachelez H, Capon F, Contreras CR, De La Cruz C, Di Meglio P, Gisondi P, Jullien D, Lambert J, Naldi L, Norton S, Puig L, Spuls P, Torres T, Warren RB, Waweru H, Weinman J, Brown MA, Galloway JB, Griffiths CM, Barker JN, Smith CH, PsoProtect study group.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2021,2021-08-19,Y,,,,,,doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render 31446406,https://doi.org/10.1136/bmjopen-2018-027577,Global health competencies in UK postgraduate medical training: a scoping review and curricular content analysis.,"Al-Shakarchi N, Obolensky L, Walpole S, Hemingway H, Banerjee A.",,BMJ open,2019,2019-08-24,Y,Global Health; Competencies; Postgraduate Medical Training,,,"

Objective

To assess global health (GH) training in all postgraduate medical education in the UK.

Design

Mixed methodology: scoping review and curricular content analysis using two GH competency frameworks.

Setting and participants

A scoping review (until December 2017) was used to develop a framework of GH competencies for doctors. National postgraduate medical training curricula were analysed against this and a prior framework for GH competencies. The number of core competencies addressed and/or appearing in each programme was recorded.

Outcomes

The scoping review identified eight relevant publications. A 16-competency framework was developed and, with a prior 5-competency framework, used to analyse each of 71 postgraduate medical curricula. Curricula were examined by a team of researchers and relevant learning outcomes were coded as one of the 5 or 16 core competencies. The number of core competencies in each programme was recorded.

Results

Using the 5-competency and 16-competency frameworks, 23 and 20, respectively, out of 71 programmes contained no global health competencies, most notably the Foundation Programme (equivalent to internship), a compulsory programme for UK medical graduates. Of a possible 16 competencies, the mean number across all 71 programmes was 1.73 (95% CI 1.42 to 2.04) and the highest number were in paediatrics and infectious diseases, each with five competencies. Of the 16 core competencies, global burden of disease and socioeconomic determinants of health were the two most cited with 47 and 35 citations, respectively. 8/16 competencies were not cited in any curriculum.

Conclusions

Equity of care and the challenges of practising in an increasingly globalised world necessitate GH competencies for all doctors. Across the whole of postgraduate training, the majority of UK doctors are receiving minimal or no training in GH. Our GH competency framework can be used to map and plan integration across postgraduate programmes.",,doi:https://doi.org/10.1136/bmjopen-2018-027577; html:https://europepmc.org/articles/PMC6720244; pdf:https://europepmc.org/articles/PMC6720244?pdf=render 35028631,https://doi.org/10.1016/s2666-7568(21)00281-6,The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care.,"Herrett E, Strongman H, Gadd S, Tomlinson L, Nitsch D, Bhaskaran K, Williamson E, van Staa T, Sofat R, Timmis A, Wells S, Smeeth L, Jackson R.",,The lancet. Healthy longevity,2022,2022-01-01,Y,,,,"

Background

For five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries. We aimed to provide descriptive data to assess the relative importance of blood pressure thresholds versus predicted risk on the subsequent rate of cardiovascular disease to inform treatment decisions.

Methods

In this English population-based cohort study, we used linked data from the Clinical Practice Research Datalink (CPRD) GOLD, Hospital Episode Statistics Admitted Patient Care, and the Office for National Statistics mortality data, and area-based deprivation indices (Townsend scores). Eligible patients were aged 30-79 years on Jan 1, 2011 (cohort entry date) and could be linked to hospital, mortality, and deprivation data. Patients were followed up until death, end of CPRD follow-up, or Nov 31, 2018. We examined three outcomes: cardiovascular disease, markers of potential target organ damage, and incident dementia without a known cause. The rate of each outcome was estimated and stratified by systolic blood pressure and predicted 10-year risk of cardiovascular disease (QRISK2 algorithm).

Findings

Between Jan 1, 2011, and Nov 31, 2018, 1 098 991 patients were included in the cohort and followed up for a median of 4·3 years (IQR 2·6-6·0; total follow-up of 4·6 million person-years). Median age at entry was 52 years (IQR 42-62) and 629 711 (57·3%) patients were female. There were 51 996 cardiovascular disease events and the overall rate of cardiovascular disease was 11·2 per 1000 person-years (95% CI 11·1-11·3). Median QRISK2 10-year predicted risk was 4·6% (IQR 1·4-12·0) and mean systolic blood pressure before cohort entry was 129·1 mm Hg (SD 15·7). Within strata of predicted risk, the effect of increasing systolic blood pressure on outcomes was small. For example, in the group with 10·0-19·9% predicted risk, rates of all cardiovascular disease rose from 20·1 to 23·6 per 1000 person-years between systolic blood pressures less than 110 mm Hg and 180 and higher mm Hg. But among patients with systolic blood pressure 140·0-149·9 mm Hg, rates rose from 6·9 to 52·3 per 1000 person-years between those with less than 10·0% risk and those with 30·0% or higher predicted risk.

Interpretation

For a wide range of blood pressures, the rate of cardiovascular disease and effectiveness of blood pressure drug treatment was mainly determined by predicted risk, with blood pressure thresholds 140/90 mm Hg or 160/100 mm Hg-ubiquitous in most countries-adding little useful information. When medium-term predicted risk is low, there is no urgency to initiate drug treatment, allowing time to attempt non-pharmacological blood pressure reduction.

Funding

National Institute for Health Research.",,doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286 -36082669,https://doi.org/10.1161/hypertensionaha.122.19354,"Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.","Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.",,"Hypertension (Dallas, Tex. : 1979)",2022,2022-09-09,Y,Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency,,,"

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.",,doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render 35579056,https://doi.org/10.1111/eci.13814,Lifestyle changes and kidney function: A 10-year follow-up study in patients with manifest cardiovascular disease.,"Østergaard HB, Demirhan I, Westerink J, Verhaar MC, Asselbergs FW, de Borst GJ, Kappelle LJ, Visseren FLJ, van der Leeuw J, UCC-SMART studygroup.",,European journal of clinical investigation,2022,2022-05-27,Y,Cardiovascular disease; Lifestyle Factors; Kidney Function Decline,,,"

Background

Patients with cardiovascular disease (CVD) are at higher risk of kidney function decline. The current study aimed to examine the association of lifestyle changes with kidney function decline in patients with manifest CVD.

Methods

A total of 2260 patients from the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort with manifest CVD who returned for a follow-up visit after a median of 9.9 years were included. The relation between change in lifestyle factors (smoking, alcohol consumption, physical activity and obesity) and change in kidney function (eGFR and uACR) was assessed using linear regression models.

Results

An increase in body mass index (β -2.81; 95% CI -3.98; -1.63 per 5 kg/m2 ) and for men also an increase in waist circumference (β -0.87; 95% CI -1.28; -0.47 per 5 cm) were significantly associated with a steeper decline in eGFR over 10 years. Continuing smoking (β -2.44, 95% CI -4.43; -0.45) and recent smoking cessation during follow-up (β -3.27; 95% CI -5.20; -1.34) were both associated with a steeper eGFR decline compared to patients who remained as non- or previous smokers from baseline. No significant association was observed between physical exercise or alcohol consumption and kidney function decline. No significant relation between any lifestyle factor and change in uACR was observed.

Conclusions

In patients with CVD, continuing smoking, recent smoking cessation and an increase in obesity markers were related to a steeper kidney function decline. Although no definite conclusions from this study can be drawn, the results support the importance of encouraging weight loss and smoking cessation in high-risk patients as a means of slowing down kidney function decline.",,doi:https://doi.org/10.1111/eci.13814; html:https://europepmc.org/articles/PMC9540114; pdf:https://europepmc.org/articles/PMC9540114?pdf=render +36082669,https://doi.org/10.1161/hypertensionaha.122.19354,"Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.","Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.",,"Hypertension (Dallas, Tex. : 1979)",2022,2022-09-09,Y,Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency,,,"

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.",,doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render 32861307,https://doi.org/10.1016/s0140-6736(20)30930-2,Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.,"Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.",,"Lancet (London, England)",2020,2020-08-01,Y,,,,"

Background

Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.

Methods

Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.

Findings

Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93).

Interpretation

The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.

Funding

NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.",,doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render 32991065,https://doi.org/10.1111/dom.14203,Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.,"Sainsbury C, Wang J, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Cooper J, Okoth K, Subramanian A, Bangash MN, Taverner T, Hanif W, Ghosh S, Narendran P, Cheng KK, Marshall T, Gkoutos G, Toulis K, Thomas N, Tahrani A, Adderley NJ, Haroon S, Nirantharakumar K.",,"Diabetes, obesity & metabolism",2021,2020-10-19,Y,Type 2 diabetes; Dpp-4 Inhibitor; Pharmaco-epidemiology; Sglt2 Inhibitor; Antidiabetic Drug,,,"Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.",,doi:https://doi.org/10.1111/dom.14203; html:https://europepmc.org/articles/PMC7537530; pdf:https://europepmc.org/articles/PMC7537530?pdf=render 35804579,https://doi.org/10.3390/ani12131679,Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.,"Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, Grinwis GCM, Szatmári V, Roelen BAJ, Vink A, van Tintelen JP, Asselbergs FW, Fieten H, Harakalova M, van Steenbeek FG.",,Animals : an open access journal from MDPI,2022,2022-06-29,Y,cardiovascular; Human Induced Pluripotent Stem Cells; Fibrofatty Infiltration; Canine Induced Pluripotent Stem Cells; Attenuated Wavy Fibers,,,"Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.",,doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render -36991119,https://doi.org/10.1038/s41586-023-05844-9,An atlas of genetic scores to predict multi-omic traits.,"Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson Å, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, Mälarstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.",,Nature,2023,2023-03-29,N,,,,"The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.",,doi:https://doi.org/10.1038/s41586-023-05844-9; pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf 34849869,https://doi.org/10.1093/gigascience/giab076,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,GigaScience,2021,2021-11-01,Y,Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2,,,"

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.",,doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render +36991119,https://doi.org/10.1038/s41586-023-05844-9,An atlas of genetic scores to predict multi-omic traits.,"Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson Å, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, Mälarstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.",,Nature,2023,2023-03-29,N,,,,"The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.",,doi:https://doi.org/10.1038/s41586-023-05844-9; pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf 36469091,https://doi.org/10.1093/ageing/afac252,Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2022,2022-12-01,N,Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes,,,"

Objective

To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.

Methods

Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.

Results

There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001).

Conclusions

Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.",,doi:https://doi.org/10.1093/ageing/afac252; pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf 37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render 35623313,https://doi.org/10.1016/j.ejrad.2022.110366,Comparison of state-of-the-art machine and deep learning algorithms to classify proximal humeral fractures using radiology text.,"Dipnall JF, Lu J, Gabbe BJ, Cosic F, Edwards E, Page R, Du L.",,European journal of radiology,2022,2022-05-20,N,Classification; Radiology; Machine Learning; Natural Language Processing; Proximal Humeral Fracture; Deep Learning; Neer; Bert,,,"

Introduction

Proximal humeral fractures account for a significant proportion of all fractures. Detailed accurate classification of the type and severity of the fracture is a key component of clinical decision making, treatment and plays an important role in orthopaedic trauma research. This research aimed to assess the performance of Machine Learning (ML) multiclass classification algorithms to classify proximal humeral fractures using radiology text data.

Materials and methods

Data from adult (16 + years) patients admitted to a major trauma centre for management of their proximal humerus fracture from January 2010 to January 2019 were used (1,324). Six input text datasets were used for classification: X-ray and/or CT scan reports (primary) and concatenation of patient age and/or patient sex. One of seven Neer class labels were classified. Models were evaluated using accuracy, recall, precision, F1, and One-versus-rest scores.

Results

A number of statistical ML algorithms performed acceptably and one of the BERT models, exhibiting good accuracy of 61% and an excellent one-versus-rest score above 0.8. The highest precision, recall and F1 scores were 50%, 39% and 39% respectively, being considered reasonable scores with the sparse text data used and in the context of machine learning.

Conclusion

ML and BERT algorithms based on routine unstructured X-ray and CT text reports, combined with the demographics of the patient, show promise in Neer classification of proximal humeral fractures to aid research. Use of these algorithms shows potential to speed up the classification task and assist radiologist, surgeons and researchers.",,doi:https://doi.org/10.1016/j.ejrad.2022.110366 -35016872,https://doi.org/10.1016/j.apmr.2021.12.014,Chronic Physical Health Conditions After Injury: A Comparison of Prevalence and Risk in People With Orthopedic Major Trauma and Other Types of Injury.,"Gelaw AY, Gabbe BJ, Ekegren CL.",,Archives of physical medicine and rehabilitation,2022,2022-01-10,N,Cardiovascular diseases; Rehabilitation; Chronic disease; wounds and injuries; Multiple Trauma,,,"

Objectives

To determine (1) the prevalence of chronic physical health conditions reported preinjury, at the time of injury, up to 1 year postinjury, and 1 to 5 years postinjury; and (2) the risk of chronic physical health conditions reported 1 to 5 years postinjury in people with orthopedic and other types of major trauma.

Design

Cohort study using linked trauma registry and health administrative datasets.

Setting

This study used linked data from the Victorian State Trauma Registry (VSTR), the Victorian Registry of Births, Deaths and Marriages (BDM), the Victorian Admitted Episodes Dataset (VAED), and the Victorian Emergency Minimum Dataset (VEMD).

Participants

Major trauma patients (N=28,522) aged 18 years and older who were registered by the VSTR, with dates of injury from 2007 to 2016, and who survived to at least 1 year after injury, were included in this study. Major trauma cases were classified into 4 groups: (1) orthopedic injury, (2) severe traumatic brain injury (s-TBI), (3) spinal cord injury, and (4) other major trauma.

Intervention

Not applicable.

Main outcome measure

Prevalence of chronic physical health conditions.

Results

The cumulative prevalence of any chronic physical health condition for all participants was 69.3%. The s-TBI group had the highest cumulative prevalence of conditions. The most common conditions were arthritis and arthropathies, cancer, and cardiovascular diseases. Preinjury chronic conditions were most common in people with s-TBI (19.3%) and were least common in people with other types of major trauma (6.6%). The highest prevalence of new-onset conditions after injury was found in people with s-TBI (21.7%) and orthopedic major trauma (21.4%), whereas the lowest prevalence was found in people with other types of major trauma (9.2%). For the orthopedic injury group, there were no significant differences in the adjusted risk of conditions reported 1 to 5 years postinjury compared with other major trauma groups.

Conclusions

Chronic physical health conditions were common among all injury groups. There was no significant difference in the risk of chronic conditions among injury groups. Rehabilitation practitioners should be aware of the risk of chronic conditions in people with orthopedic and other types of major trauma. Long-term follow-up care after injury should include prevention and treatment of chronic conditions.",,doi:https://doi.org/10.1016/j.apmr.2021.12.014 31558464,https://doi.org/10.1136/bmjopen-2019-033013,Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge G, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,BMJ open,2019,2019-09-26,Y,Child; Asthma; Caesarean section; Eczema; Antibiotic Prophylaxis; Immune System Diseases,,,"

Introduction

In the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health.

Methods and analysis

A controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006-2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level.

Ethics and dissemination

Ethical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.",,doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render +35016872,https://doi.org/10.1016/j.apmr.2021.12.014,Chronic Physical Health Conditions After Injury: A Comparison of Prevalence and Risk in People With Orthopedic Major Trauma and Other Types of Injury.,"Gelaw AY, Gabbe BJ, Ekegren CL.",,Archives of physical medicine and rehabilitation,2022,2022-01-10,N,Cardiovascular diseases; Rehabilitation; Chronic disease; wounds and injuries; Multiple Trauma,,,"

Objectives

To determine (1) the prevalence of chronic physical health conditions reported preinjury, at the time of injury, up to 1 year postinjury, and 1 to 5 years postinjury; and (2) the risk of chronic physical health conditions reported 1 to 5 years postinjury in people with orthopedic and other types of major trauma.

Design

Cohort study using linked trauma registry and health administrative datasets.

Setting

This study used linked data from the Victorian State Trauma Registry (VSTR), the Victorian Registry of Births, Deaths and Marriages (BDM), the Victorian Admitted Episodes Dataset (VAED), and the Victorian Emergency Minimum Dataset (VEMD).

Participants

Major trauma patients (N=28,522) aged 18 years and older who were registered by the VSTR, with dates of injury from 2007 to 2016, and who survived to at least 1 year after injury, were included in this study. Major trauma cases were classified into 4 groups: (1) orthopedic injury, (2) severe traumatic brain injury (s-TBI), (3) spinal cord injury, and (4) other major trauma.

Intervention

Not applicable.

Main outcome measure

Prevalence of chronic physical health conditions.

Results

The cumulative prevalence of any chronic physical health condition for all participants was 69.3%. The s-TBI group had the highest cumulative prevalence of conditions. The most common conditions were arthritis and arthropathies, cancer, and cardiovascular diseases. Preinjury chronic conditions were most common in people with s-TBI (19.3%) and were least common in people with other types of major trauma (6.6%). The highest prevalence of new-onset conditions after injury was found in people with s-TBI (21.7%) and orthopedic major trauma (21.4%), whereas the lowest prevalence was found in people with other types of major trauma (9.2%). For the orthopedic injury group, there were no significant differences in the adjusted risk of conditions reported 1 to 5 years postinjury compared with other major trauma groups.

Conclusions

Chronic physical health conditions were common among all injury groups. There was no significant difference in the risk of chronic conditions among injury groups. Rehabilitation practitioners should be aware of the risk of chronic conditions in people with orthopedic and other types of major trauma. Long-term follow-up care after injury should include prevention and treatment of chronic conditions.",,doi:https://doi.org/10.1016/j.apmr.2021.12.014 PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated with multi-mode transportation networks in China,"Xu X, Liu X, Wang L, Wu Y, Lu X, Wang X, Pei S.",,Fundamental Research,2022,2022-04-22,Y,Complex Network; Spatial Spread; Human Mobility; Transportation Networks; Covid-19,,,"The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses. Graphical abstract Image, graphical abstract.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9023380; pdf:https://europepmc.org/articles/PMC9023380?pdf=render 34306597,https://doi.org/10.1155/2021/6663884,Automatic Prediction of Recurrence of Major Cardiovascular Events: A Text Mining Study Using Chest X-Ray Reports.,"Bagheri A, Groenhof TKJ, Asselbergs FW, Haitjema S, Bots ML, Veldhuis WB, de Jong PA, Oberski DL.",,Journal of healthcare engineering,2021,2021-07-09,Y,,,,"

Methods

We used EHR data of patients included in the Second Manifestations of ARTerial disease (SMART) study. We propose a deep learning-based multimodal architecture for our text mining pipeline that integrates neural text representation with preprocessed clinical predictors for the prediction of recurrence of major cardiovascular events in cardiovascular patients. Text preprocessing, including cleaning and stemming, was first applied to filter out the unwanted texts from X-ray radiology reports. Thereafter, text representation methods were used to numerically represent unstructured radiology reports with vectors. Subsequently, these text representation methods were added to prediction models to assess their clinical relevance. In this step, we applied logistic regression, support vector machine (SVM), multilayer perceptron neural network, convolutional neural network, long short-term memory (LSTM), and bidirectional LSTM deep neural network (BiLSTM).

Results

We performed various experiments to evaluate the added value of the text in the prediction of major cardiovascular events. The two main scenarios were the integration of radiology reports (1) with classical clinical predictors and (2) with only age and sex in the case of unavailable clinical predictors. In total, data of 5603 patients were used with 5-fold cross-validation to train the models. In the first scenario, the multimodal BiLSTM (MI-BiLSTM) model achieved an area under the curve (AUC) of 84.7%, misclassification rate of 14.3%, and F1 score of 83.8%. In this scenario, the SVM model, trained on clinical variables and bag-of-words representation, achieved the lowest misclassification rate of 12.2%. In the case of unavailable clinical predictors, the MI-BiLSTM model trained on radiology reports and demographic (age and sex) variables reached an AUC, F1 score, and misclassification rate of 74.5%, 70.8%, and 20.4%, respectively.

Conclusions

Using the case study of routine care chest X-ray radiology reports, we demonstrated the clinical relevance of integrating text features and classical predictors in our text mining pipeline for cardiovascular risk prediction. The MI-BiLSTM model with word embedding representation appeared to have a desirable performance when trained on text data integrated with the clinical variables from the SMART study. Our results mined from chest X-ray reports showed that models using text data in addition to laboratory values outperform those using only known clinical predictors.",,doi:https://doi.org/10.1155/2021/6663884; html:https://europepmc.org/articles/PMC8285182; pdf:https://europepmc.org/articles/PMC8285182?pdf=render -37198662,https://doi.org/10.1186/s13293-023-00516-9,Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure.,"de Bakker M, Petersen TB, Akkerhuis KM, Harakalova M, Umans VA, Germans T, Caliskan K, Katsikis PD, van der Spek PJ, Suthahar N, de Boer RA, Rizopoulos D, Asselbergs FW, Boersma E, Kardys I.",,Biology of sex differences,2023,2023-05-17,Y,Proteomics; Sex differences; Heart Failure; Hfref,,,"

Background

Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.

Methods

In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13-31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.

Results

In 104 women and 278 men (mean age 62 and 64 years, respectively) cumulative PEP incidence at 30 months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction < 0.001) and somatostatin (Pinteraction = 0.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p < 0.001) compared to women (1.14 [1.01, 1.29], p = 0.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p < 0.001), but inversely associated in women (0.33 [0.12, 0.93], p = 0.036).

Conclusion

Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.",,doi:https://doi.org/10.1186/s13293-023-00516-9; html:https://europepmc.org/articles/PMC10193800; pdf:https://europepmc.org/articles/PMC10193800?pdf=render 32929109,https://doi.org/10.1038/s41598-020-72060-0,A data-driven typology of asthma medication adherence using cluster analysis.,"Tibble H, Chan A, Mitchell EA, Horne E, Doudesis D, Horne R, Mizani MA, Sheikh A, Tsanas A.",,Scientific reports,2020,2020-09-14,Y,,,,"Asthma preventer medication non-adherence is strongly associated with poor asthma control. One-dimensional measures of adherence may ignore clinically important patterns of medication-taking behavior. We sought to construct a data-driven multi-dimensional typology of medication non-adherence in children with asthma. We analyzed data from an intervention study of electronic inhaler monitoring devices, comprising 211 patients yielding 35,161 person-days of data. Five adherence measures were extracted: the percentage of doses taken, the percentage of days on which zero doses were taken, the percentage of days on which both doses were taken, the number of treatment intermissions per 100 study days, and the duration of treatment intermissions per 100 study days. We applied principal component analysis on the measures and subsequently applied k-means to determine cluster membership. Decision trees identified the measure that could predict cluster assignment with the highest accuracy, increasing interpretability and increasing clinical utility. We demonstrate the use of adherence measures towards a three-group categorization of medication non-adherence, which succinctly describes the diversity of patient medication taking patterns in asthma. The percentage of prescribed doses taken during the study contributed to the prediction of cluster assignment most accurately (84% in out-of-sample data).",,doi:https://doi.org/10.1038/s41598-020-72060-0; html:https://europepmc.org/articles/PMC7490405; pdf:https://europepmc.org/articles/PMC7490405?pdf=render +37198662,https://doi.org/10.1186/s13293-023-00516-9,Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure.,"de Bakker M, Petersen TB, Akkerhuis KM, Harakalova M, Umans VA, Germans T, Caliskan K, Katsikis PD, van der Spek PJ, Suthahar N, de Boer RA, Rizopoulos D, Asselbergs FW, Boersma E, Kardys I.",,Biology of sex differences,2023,2023-05-17,Y,Proteomics; Sex differences; Heart Failure; Hfref,,,"

Background

Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.

Methods

In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13-31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.

Results

In 104 women and 278 men (mean age 62 and 64 years, respectively) cumulative PEP incidence at 30 months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction < 0.001) and somatostatin (Pinteraction = 0.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p < 0.001) compared to women (1.14 [1.01, 1.29], p = 0.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p < 0.001), but inversely associated in women (0.33 [0.12, 0.93], p = 0.036).

Conclusion

Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.",,doi:https://doi.org/10.1186/s13293-023-00516-9; html:https://europepmc.org/articles/PMC10193800; pdf:https://europepmc.org/articles/PMC10193800?pdf=render 37422075,https://doi.org/10.1016/j.jval.2023.06.019,Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.,"King-Kallimanis BL, Calvert M, Cella D, Cocks K, Coens C, Fairclough D, Howie L, Jonsson P, Mahendraratnam N, Maues J, Sarac S, Shaw J, Stigger N, Trask P, Wieseler B.",,Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research,2023,2023-07-06,N,Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective,,,"

Objectives

Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue.

Methods

We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development.

Results

Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.

Conclusions

Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.",,doi:https://doi.org/10.1016/j.jval.2023.06.019 33328048,https://doi.org/10.1016/s2589-7500(20)30218-1,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.,"Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,N,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders), and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,doi:https://doi.org/10.1016/S2589-7500(20)30218-1; html:https://europepmc.org/articles/PMC8183333; pdf:https://europepmc.org/articles/PMC8183333?pdf=render; doi:https://doi.org/10.1016/s2589-7500(20)30218-1 -35587337,https://doi.org/10.1093/ije/dyac105,"Gestational age at birth, chronic conditions and school outcomes: a population-based data linkage study of children born in England. ","Libuy N, Gilbert R, Mc Grath-Lone L, Blackburn R, Etoori D, Harron K.",,International journal of epidemiology,2023,2023-02-01,Y,,,,"We aimed to generate evidence about child development measured through school attainment and provision of special educational needs (SEN) across the spectrum of gestational age, including for children born early term and >41 weeks of gestation, with and without chronic health conditions. We used a national linked dataset of hospital and education records of children born in England between 1 September 2004 and 31 August 2005. We evaluated school attainment at Key Stage 1 (KS1; age 7) and Key Stage 2 (KS2; age 11) and any SEN by age 11. We stratified analyses by chronic health conditions up to age 2, and size-for-gestation, and calculated population attributable fractions (PAF). Of 306 717 children, 5.8% were born <37 weeks gestation and 7.0% had a chronic condition. The percentage of children not achieving the expected level at KS1 increased from 7.6% at 41 weeks, to 50.0% at 24 weeks of gestation. A similar pattern was seen at KS2. SEN ranged from 29.0% at 41 weeks to 82.6% at 24 weeks. Children born early term (37-38 weeks of gestation) had poorer outcomes than those born at 40 weeks; 3.2% of children with SEN were attributable to having a chronic condition compared with 2.0% attributable to preterm birth. Children born with early identified chronic conditions contribute more to the burden of poor school outcomes than preterm birth. Evaluation is needed of how early health characteristics can be used to improve preparation for education, before and at entry to school.",,doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render 34948912,https://doi.org/10.3390/ijerph182413304,Development and Validation of a Primary Care Electronic Health Record Phenotype to Study Migration and Health in the UK.,"Pathak N, Zhang CX, Boukari Y, Burns R, Mathur R, Gonzalez-Izquierdo A, Denaxas S, Sonnenberg P, Hayward A, Aldridge RW.",,International journal of environmental research and public health,2021,2021-12-17,Y,Migration; Phenotype; Validation; Algorithm; Primary Care; Clinical Practice Research Datalink,,,"International migrants comprised 14% of the UK's population in 2020; however, their health is rarely studied at a population level using primary care electronic health records due to difficulties in their identification. We developed a migration phenotype using country of birth, visa status, non-English main/first language and non-UK-origin codes and applied it to the Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country-of-birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997 to 2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified: 178,749 (1.11%) had foreign-country-of-birth or visa -status codes, 216,731 (1.35%) non-English-main/first-language codes, and 8288 (0.05%) non-UK-origin codes. The cohort was similarly distributed versus ONS data by sex and region of birth. Migration recording improved over time and younger migrants were better represented than those aged ≥50. The validated phenotype identified a large migrant cohort for use in migration health research in CPRD GOLD to inform healthcare policy and practice. The under-recording of migration status in earlier years and older ages necessitates cautious interpretation of future studies in these groups.",,doi:https://doi.org/10.3390/ijerph182413304; html:https://europepmc.org/articles/PMC8707886; pdf:https://europepmc.org/articles/PMC8707886?pdf=render +35587337,https://doi.org/10.1093/ije/dyac105,"Gestational age at birth, chronic conditions and school outcomes: a population-based data linkage study of children born in England. ","Libuy N, Gilbert R, Mc Grath-Lone L, Blackburn R, Etoori D, Harron K.",,International journal of epidemiology,2023,2023-02-01,Y,,,,"We aimed to generate evidence about child development measured through school attainment and provision of special educational needs (SEN) across the spectrum of gestational age, including for children born early term and >41 weeks of gestation, with and without chronic health conditions. We used a national linked dataset of hospital and education records of children born in England between 1 September 2004 and 31 August 2005. We evaluated school attainment at Key Stage 1 (KS1; age 7) and Key Stage 2 (KS2; age 11) and any SEN by age 11. We stratified analyses by chronic health conditions up to age 2, and size-for-gestation, and calculated population attributable fractions (PAF). Of 306 717 children, 5.8% were born <37 weeks gestation and 7.0% had a chronic condition. The percentage of children not achieving the expected level at KS1 increased from 7.6% at 41 weeks, to 50.0% at 24 weeks of gestation. A similar pattern was seen at KS2. SEN ranged from 29.0% at 41 weeks to 82.6% at 24 weeks. Children born early term (37-38 weeks of gestation) had poorer outcomes than those born at 40 weeks; 3.2% of children with SEN were attributable to having a chronic condition compared with 2.0% attributable to preterm birth. Children born with early identified chronic conditions contribute more to the burden of poor school outcomes than preterm birth. Evaluation is needed of how early health characteristics can be used to improve preparation for education, before and at entry to school.",,doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render 34038519,https://doi.org/10.1093/ageing/afab084,Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,Age and ageing,2021,2021-09-01,Y,Recruitment; Older People; Registry; Sarcopenia,,,"

Background

sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population.

Methods

six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates.

Results

sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies.

Conclusion

recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.",,doi:https://doi.org/10.1093/ageing/afab084; html:https://europepmc.org/articles/PMC8437066; pdf:https://europepmc.org/articles/PMC8437066?pdf=render 34409990,https://doi.org/10.1093/dote/doab058,Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia. ,"Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",,Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus,2022,2022-01-01,N,,,,"We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",,doi:https://doi.org/10.1093/dote/doab058; pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf 36828609,https://doi.org/10.1016/s2589-7500(22)00252-7,Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.,"Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",,doi:https://doi.org/10.1016/S2589-7500(22)00252-7 -36722341,https://doi.org/10.1093/cei/uxad008,Practical challenges for functional validation of STAT1 gain of function genetic variants.,"Albuquerque AS, Maimaris J, McKenna AJ, Lambourne J, Moreira F, Workman S, Megy K, Simeoni I, Lango Allen H, NIHR BioResource-Rare Disease Consortium, Morris EC, Burns SO.",,Clinical and experimental immunology,2023,2023-04-01,Y,Flow cytometry; STAT1; Primary Immunodeficiency; Gain Of Function; Chronic Mucocutaneous Candidiasis; Variants Of Unknown Significance,,,,,doi:https://doi.org/10.1093/cei/uxad008; html:https://europepmc.org/articles/PMC10128160; pdf:https://europepmc.org/articles/PMC10128160?pdf=render 33830993,https://doi.org/10.1371/journal.pgen.1009428,Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, Strawbridge RJ, Price TJ, Smith DJ, Nicholl BI, Bailey MES.",,PLoS genetics,2021,2021-04-08,Y,,,,"Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.",,doi:https://doi.org/10.1371/journal.pgen.1009428; html:https://europepmc.org/articles/PMC8031124; pdf:https://europepmc.org/articles/PMC8031124?pdf=render +36722341,https://doi.org/10.1093/cei/uxad008,Practical challenges for functional validation of STAT1 gain of function genetic variants.,"Albuquerque AS, Maimaris J, McKenna AJ, Lambourne J, Moreira F, Workman S, Megy K, Simeoni I, Lango Allen H, NIHR BioResource-Rare Disease Consortium, Morris EC, Burns SO.",,Clinical and experimental immunology,2023,2023-04-01,Y,Flow cytometry; STAT1; Primary Immunodeficiency; Gain Of Function; Chronic Mucocutaneous Candidiasis; Variants Of Unknown Significance,,,,,doi:https://doi.org/10.1093/cei/uxad008; html:https://europepmc.org/articles/PMC10128160; pdf:https://europepmc.org/articles/PMC10128160?pdf=render 32856398,https://doi.org/10.1111/1742-6723.13604,To intubate or not to intubate? Predictors of inhalation injury in burn-injured patients before arrival at the burn centre.,"Dyson K, Baker P, Garcia N, Braun A, Aung M, Pilcher D, Smith K, Cleland H, Gabbe B.",,Emergency medicine Australasia : EMA,2021,2020-08-27,N,Burn; Pre-hospital; Inhalation Injury; Endotracheal Intubation,,,"

Objective

Inhalation injury occurs in approximately 10-20% of burn patients and is associated with increased mortality. There is no clear method of identifying patients at risk of inhalation injury or requiring intubation in the pre-hospital setting. Our objective was to identify pre-burn centre factors associated with inhalation injury confirmed on bronchoscopy, and to develop a prognostic model for inhalation injury.

Methods

We analysed acute admissions from the Victorian Adult Burns Service and Ambulance Victoria electronic patient care records for 1 July 2009 to 30 June 2016. We defined inhalation injury as an Abbreviated Injury Scale of >1 on bronchoscopy. A multivariable logistic regression prediction model was developed based on pre-burn centre factors.

Results

Emergency medical services transported 1148 patients who were admitted to the burn centre. The median age of patients was 39 years and most patients had <10% total body surface area (%TBSA) burned. The prevalence of confirmed inhalation injury was 11%. Increasing %TBSA burned, flame, enclosed space, face burns, hoarse voice, soot in mouth and shortness of breath were predictive of inhalation injury. The model provided excellent discrimination (area under curve 0.87, 95% confidence interval 0.84-0.91). A lower proportion of patients intubated at a non-burn centre had an inhalation injury (33%) compared to patients intubated by emergency medical services (54%) and in the burn centre (58%).

Conclusions

A model to predict inhalation injury in burn-injured patients was developed with excellent discrimination. This model requires prospective testing but could form an integral part of clinician decision-making.",,doi:https://doi.org/10.1111/1742-6723.13604 36273236,https://doi.org/10.1038/s41746-022-00705-7,"Automated clinical coding: what, why, and where we are?","Dong H, Falis M, Whiteley W, Alex B, Matterson J, Ji S, Chen J, Wu H.",,NPJ digital medicine,2022,2022-10-22,Y,,,,"Clinical coding is the task of transforming medical information in a patient's health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019-early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond.",,doi:https://doi.org/10.1038/s41746-022-00705-7; html:https://europepmc.org/articles/PMC9588058; pdf:https://europepmc.org/articles/PMC9588058?pdf=render 32426117,https://doi.org/10.7189/jogh.10.010348,Novel approaches to estimate compliance with lockdown measures in the COVID-19 pandemic.,"Sheikh A, Sheikh Z, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,This is a summary of new methods for estimating phyiscal distancing and compliance with lockdown. I haven't scored the content because it isn't primary research.,doi:https://doi.org/10.7189/jogh.10.010348; html:https://europepmc.org/articles/PMC7211415; pdf:https://europepmc.org/articles/PMC7211415?pdf=render 37180793,https://doi.org/10.3389/fcvm.2023.1136764,Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.,"Chadalavada S, Reinikainen J, Andersson J, Di Castelnuovo A, Iacoviello L, Jousilahti P, Kårhus LL, Linneberg A, Söderberg S, Tunstall-Pedoe H, Lekadir K, Aung N, Jensen MT, Kuulasmaa K, Niiranen TJ, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-04-25,Y,Diabetes; Sex differences; epidemiology; Heart Failure; Morgam,,,"

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.",,doi:https://doi.org/10.3389/fcvm.2023.1136764; html:https://europepmc.org/articles/PMC10167048; pdf:https://europepmc.org/articles/PMC10167048?pdf=render -35743743,https://doi.org/10.3390/jpm12060958,Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.,"Vo DHT, McGleave G, Overton IM.",,Journal of personalized medicine,2022,2022-06-11,Y,Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology,,,"The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.",,doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render 34378227,https://doi.org/10.1111/tri.14010,"Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.","McKay SC, Lembach H, Hann A, Okoth K, Anderton J, Nirantharakumar K, Magill L, Torlinska B, Armstrong M, Mascaro J, Inston N, Pinkney T, Ranasinghe A, Borrows R, Ferguson J, Isaac J, Calvert M, Perera MTPR, Hartog H.",,Transplant international : official journal of the European Society for Organ Transplantation,2021,2021-09-16,Y,Isolation; Transplant; Mental health; Health-related Quality Of Life; Shielding; Covid-19,,,"Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.",,doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?pdf=render -34734970,https://doi.org/10.1001/jamaophthalmol.2021.4601,"Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.","Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).",,JAMA ophthalmology,2021,2021-12-01,Y,,,,"

Importance

Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.

Objective

To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.

Design, setting, participants

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.

Exposures

Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.

Main outcomes and measures

Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

Results

A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Conclusions and relevance

This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.",,doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599 +35743743,https://doi.org/10.3390/jpm12060958,Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.,"Vo DHT, McGleave G, Overton IM.",,Journal of personalized medicine,2022,2022-06-11,Y,Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology,,,"The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.",,doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render 30183734,https://doi.org/10.1371/journal.pone.0202359,Time spent at blood pressure target and the risk of death and cardiovascular diseases.,"Chung SC, Pujades-Rodriguez M, Duyx B, Denaxas SC, Pasea L, Hingorani A, Timmis A, Williams B, Hemingway H.",,PloS one,2018,2018-09-05,Y,,The Human Phenome,,"

Background

The time a patient spends with blood pressure at target level is an intuitive measure of successful BP management, but population studies on its effectiveness are as yet unavailable.

Method

We identified a population-based cohort of 169,082 individuals with newly identified high blood pressure who were free of cardiovascular disease from January 1997 to March 2010. We used 1.64 million clinical blood pressure readings to calculate the TIme at TaRgEt (TITRE) based on current target blood pressure levels.

Result

The median (Inter-quartile range) TITRE among all patients was 2.8 (0.3, 5.6) months per year, only 1077 (0.6%) patients had a TITRE ≥11 months. Compared to people with a 0% TITRE, patients with a TITRE of 3-5.9 months, and 6-8.9 months had 75% and 78% lower odds of the composite of cardiovascular death, myocardial infarction and stroke (adjusted odds ratios, 0.25 (95% confidence interval: 0.21, 0.31) and 0.22 (0.17, 0.27), respectively). These associations were consistent for heart failure and any cardiovascular disease and death (comparing a 3-5.9 month to 0% TITRE, 63% and 60% lower in odds, respectively), among people who did or did not have blood pressure 'controlled' on a single occasion during the first year of follow-up, and across groups defined by number of follow-up BP measure categories.

Conclusion

Based on the current frequency of measurement of blood pressure this study suggests that few newly hypertensive patients sustained a complete, year-round on target blood pressure over time. The inverse associations between a higher TITRE and lower risk of incident cardiovascular diseases were independent of widely-used blood pressure 'control' indicators. Randomized trials are required to evaluate interventions to increase a person's time spent at blood pressure target.",,doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render +34734970,https://doi.org/10.1001/jamaophthalmol.2021.4601,"Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.","Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).",,JAMA ophthalmology,2021,2021-12-01,Y,,,,"

Importance

Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.

Objective

To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.

Design, setting, participants

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.

Exposures

Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.

Main outcomes and measures

Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

Results

A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Conclusions and relevance

This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.",,doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599 36689332,https://doi.org/10.1093/neuonc/noad021,GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.,"Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF.",,Neuro-oncology,2023,2023-07-01,Y,Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics,,,"

Background

Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

Methods

We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best.

Results

Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.

Conclusions

GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render 32352158,https://doi.org/10.1002/bjs.11580,Author response to: Comment on: Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.,"Adderley N, Singh P, Tahrani AA, Nirantharakumar K.",,The British journal of surgery,2020,2020-04-30,N,,,,,,doi:https://doi.org/10.1002/bjs.11580 33560181,https://doi.org/10.1177/0272989x21994035,The Value of Triage during Periods of Intense COVID-19 Demand: Simulation Modeling Study.,"Wood RM, Pratt AC, Kenward C, McWilliams CJ, Booton RD, Thomas MJ, Bourdeaux CP, Vasilakis C.",,Medical decision making : an international journal of the Society for Medical Decision Making,2021,2021-02-09,N,Computer simulation; Coronavirus; Intensive Care; Critical Care; Triage; Covid-19,,,"

Background

During the COVID-19 pandemic, many intensive care units have been overwhelmed by unprecedented levels of demand. Notwithstanding ethical considerations, the prioritization of patients with better prognoses may support a more effective use of available capacity in maximizing aggregate outcomes. This has prompted various proposed triage criteria, although in none of these has an objective assessment been made in terms of impact on number of lives and life-years saved.

Design

An open-source computer simulation model was constructed for approximating the intensive care admission and discharge dynamics under triage. The model was calibrated from observational data for 9505 patient admissions to UK intensive care units. To explore triage efficacy under various conditions, scenario analysis was performed using a range of demand trajectories corresponding to differing nonpharmaceutical interventions.

Results

Triaging patients at the point of expressed demand had negligible effect on deaths but reduces life-years lost by up to 8.4% (95% confidence interval: 2.6% to 18.7%). Greater value may be possible through ""reverse triage"", that is, promptly discharging any patient not meeting the criteria if admission cannot otherwise be guaranteed for one who does. Under such policy, life-years lost can be reduced by 11.7% (2.8% to 25.8%), which represents 23.0% (5.4% to 50.1%) of what is operationally feasible with no limit on capacity and in the absence of improved clinical treatments.

Conclusions

The effect of simple triage is limited by a tradeoff between reduced deaths within intensive care (due to improved outcomes) and increased deaths resulting from declined admission (due to lower throughput given the longer lengths of stay of survivors). Improvements can be found through reverse triage, at the expense of potentially complex ethical considerations.",,doi:https://doi.org/10.1177/0272989X21994035 @@ -1157,9 +1160,9 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33240510,https://doi.org/10.15420/aer.2020.26,Big Data and Artificial Intelligence: Opportunities and Threats in Electrophysiology.,"van de Leur RR, Boonstra MJ, Bagheri A, Roudijk RW, Sammani A, Taha K, Doevendans PA, van der Harst P, van Dam PM, Hassink RJ, van Es R, Asselbergs FW.",,Arrhythmia & electrophysiology review,2020,2020-11-01,Y,Artificial intelligence; Electrophysiology; Neural networks; ECG; Cardiology; Big Data; Deep Learning,,,"The combination of big data and artificial intelligence (AI) is having an increasing impact on the field of electrophysiology. Algorithms are created to improve the automated diagnosis of clinical ECGs or ambulatory rhythm devices. Furthermore, the use of AI during invasive electrophysiological studies or combining several diagnostic modalities into AI algorithms to aid diagnostics are being investigated. However, the clinical performance and applicability of created algorithms are yet unknown. In this narrative review, opportunities and threats of AI in the field of electrophysiology are described, mainly focusing on ECGs. Current opportunities are discussed with their potential clinical benefits as well as the challenges. Challenges in data acquisition, model performance, (external) validity, clinical implementation, algorithm interpretation as well as the ethical aspects of AI research are discussed. This article aims to guide clinicians in the evaluation of new AI applications for electrophysiology before their clinical implementation.",,doi:https://doi.org/10.15420/aer.2020.26; html:https://europepmc.org/articles/PMC7675143; pdf:https://europepmc.org/articles/PMC7675143?pdf=render 31302040,https://doi.org/10.1016/j.jchf.2019.03.009,Risk for Heart Failure: The Opportunity for Prevention With the American Heart Association's Life's Simple 7.,"Uijl A, Koudstaal S, Vaartjes I, Boer JMA, Verschuren WMM, van der Schouw YT, Asselbergs FW, Hoes AW, Sluijs I.",,JACC. Heart failure,2019,2019-07-10,N,Heart Failure; Cardiovascular Disease Risk Factors; Healthy Lifestyle; Life’s Simple 7,,,"

Objectives

The aim of this study is to determine whether combinations of specific Life's Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).

Background

The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.

Methods

A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.

Results

Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.

Conclusions

A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.",,doi:https://doi.org/10.1016/j.jchf.2019.03.009 33289226,https://doi.org/10.1111/ans.16426,Association between gender and outcomes of acute burns patients. ,"Perkins M, Abesamis GM, Cleland H, Gabbe BJ, Tracy LM.",,ANZ journal of surgery,2020,2020-12-01,N,,,,"Burn injuries are a complex and serious public health concern. Where the total body surface area of the burn exceeds 50%, mortality rates as high as 48% have been reported. While the association between gender and burn injury outcomes has been explored, findings are inconsistent. Adult patients (>15 years) admitted between 1 July 2009 and 30 June 2018 to intensive care units of burn centres that provide specialist burn care in Australia and New Zealand were included. Raw mortality rates were examined and a multivariable Cox proportional hazards regression was used to investigate the association between gender and time to in-hospital death. There were 2227 eligible burn injury admissions. Men comprised the majority (77.6%). The proportion of women who died in hospital was greater than men and the adjusted odds of in-hospital mortality were 34% lower in men (odds ratio 0.66; 95% confidence interval (CI) 0.45-0.98). The unadjusted rate of in-hospital mortality for men was 44% lower than women (hazard ratio 0.56; 95% CI 0.41-0.76). After adjusting for confounders, there was no association between gender and survival time (hazard ratio 0.76; 95% CI 0.54-1.06). After adjustment for key differences in case-mix between men and women, there was an association between gender and in-hospital mortality and no association between gender and time to death. Our findings indicate that the worse outcomes observed for women are associated with different age and patterns of injury, and provide further information to direct and inform targeted prevention measures for vulnerable populations.",,doi:https://doi.org/10.1111/ans.16426 +34761838,https://doi.org/10.1002/biof.1801,Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study.,"Mannarino MR, Bianconi V, Gigante B, Strawbridge RJ, Savonen K, Kurl S, Giral P, Smit A, Eriksson P, Tremoli E, Veglia F, Baldassarre D, Pirro M, IMPROVE study group.",,"BioFactors (Oxford, England)",2022,2021-11-11,Y,Lymphocyte; neutrophil; cardiovascular; Carotid; Prospective; Imt; Nlr,,,"Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.",,doi:https://doi.org/10.1002/biof.1801; html:https://europepmc.org/articles/PMC9299016; pdf:https://europepmc.org/articles/PMC9299016?pdf=render 35297548,https://doi.org/10.1002/humu.24369,"Beacon v2 and Beacon networks: A ""lingua franca"" for federated data discovery in biomedical genomics, and beyond.","Rambla J, Baudis M, Ariosa R, Beck T, Fromont LA, Navarro A, Paloots R, Rueda M, Saunders G, Singh B, Spalding JD, Törnroos J, Vasallo C, Veal CD, Brookes AJ.",,Human mutation,2022,2022-04-08,Y,data sharing; Clinical Genomics; Beacon; Data Discovery; Rest Api; Ga4gh,,,"Beacon is a basic data discovery protocol issued by the Global Alliance for Genomics and Health (GA4GH). The main goal addressed by version 1 of the Beacon protocol was to test the feasibility of broadly sharing human genomic data, through providing simple ""yes"" or ""no"" responses to queries about the presence of a given variant in datasets hosted by Beacon providers. The popularity of this concept has fostered the design of a version 2, that better serves real-world requirements and addresses the needs of clinical genomics research and healthcare, as assessed by several contributing projects and organizations. Particularly, rare disease genetics and cancer research will benefit from new case level and genomic variant level requests and the enabling of richer phenotype and clinical queries as well as support for fuzzy searches. Beacon is designed as a ""lingua franca"" to bridge data collections hosted in software solutions with different and rich interfaces. Beacon version 2 works alongside popular standards like Phenopackets, OMOP, or FHIR, allowing implementing consortia to return matches in beacon responses and provide a handover to their preferred data exchange format. The protocol is being explored by other research domains and is being tested in several international projects.",,doi:https://doi.org/10.1002/humu.24369; html:https://europepmc.org/articles/PMC9322265; pdf:https://europepmc.org/articles/PMC9322265?pdf=render 34850874,https://doi.org/10.1093/gigascience/giab083,Erratum to: An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis. ,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, Collaborative NCCID.",,GigaScience,2021,2021-12-01,Y,,,,,,doi:https://doi.org/10.1093/gigascience/giab083; html:https://europepmc.org/articles/PMC8634578; pdf:https://europepmc.org/articles/PMC8634578?pdf=render -34761838,https://doi.org/10.1002/biof.1801,Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study.,"Mannarino MR, Bianconi V, Gigante B, Strawbridge RJ, Savonen K, Kurl S, Giral P, Smit A, Eriksson P, Tremoli E, Veglia F, Baldassarre D, Pirro M, IMPROVE study group.",,"BioFactors (Oxford, England)",2022,2021-11-11,Y,Lymphocyte; neutrophil; cardiovascular; Carotid; Prospective; Imt; Nlr,,,"Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.",,doi:https://doi.org/10.1002/biof.1801; html:https://europepmc.org/articles/PMC9299016; pdf:https://europepmc.org/articles/PMC9299016?pdf=render 34772649,https://doi.org/10.1016/s2589-7500(21)00252-1,Characteristics of publicly available skin cancer image datasets: a systematic review.,"Wen D, Khan SM, Ji Xu A, Ibrahim H, Smith L, Caballero J, Zepeda L, de Blas Perez C, Denniston AK, Liu X, Matin RN.",,The Lancet. Digital health,2022,2021-11-09,N,,,,"Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed.",,doi:https://doi.org/10.1016/S2589-7500(21)00252-1 33531486,https://doi.org/10.1038/s41467-021-21370-6,Author Correction: Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2021,2021-02-02,Y,,,,,,doi:https://doi.org/10.1038/s41467-021-21370-6; html:https://europepmc.org/articles/PMC7854714; pdf:https://europepmc.org/articles/PMC7854714?pdf=render 35089148,https://doi.org/10.2196/28095,The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.,"Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Siddi S, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, RADAR-CNS.",,JMIR mHealth and uHealth,2022,2022-01-28,Y,GPS; Mobile phone; Major Depressive Disorder; Smartphone; Phq-8; Home Stay,,,"

Background

Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.

Objective

The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.

Methods

We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigación Biomédica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.

Results

Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).

Conclusions

Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.",,doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593 @@ -1169,11 +1172,11 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 32379357,https://doi.org/10.1002/sim.8563,A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data.,"Carragher R, Mueller T, Bennie M, Robertson C.",,Statistics in medicine,2020,2020-05-07,N,Observational Study; Multiple Outcomes; Direct Oral Anticoagulants; Safety Outcomes; Bayesian Hierarchy,,,"Clinical trials are the standard approach for evaluating new treatments, but may lack the power to assess rare outcomes. Trial results are also necessarily restricted to the population considered in the study. The availability of routinely collected healthcare data provides a source of information on the performance of treatments beyond that offered by clinical trials, but the analysis of this type of data presents a number of challenges. Hierarchical methods, which take advantage of known relationships between clinical outcomes, while accounting for bias, may be a suitable statistical approach for the analysis of this data. A study of direct oral anticoagulants in Scotland is discussed and used to motivate a modeling approach. A Bayesian hierarchical model, which allows a stratification of the population into clusters with similar characteristics, is proposed and applied to the direct oral anticoagulant study data. A simulation study is used to assess its performance in terms of outcome detection and error rates.",,doi:https://doi.org/10.1002/sim.8563; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8563 36819459,https://doi.org/10.1210/jendso/bvad020,"Polygenic Risk of Prediabetes, Undiagnosed Diabetes, and Incident Type 2 Diabetes Stratified by Diabetes Risk Factors.","Liu X, Collister JA, Clifton L, Hunter DJ, Littlejohns TJ.",,Journal of the Endocrine Society,2023,2023-01-30,Y,BMI; Family History; Polygenic Risk And Diabetes,,,"

Context

Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.

Objective

This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.

Methods

We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRST2D) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.

Results

At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRST2D with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRST2D with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRST2D and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRST2D.

Conclusion

Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.",,doi:https://doi.org/10.1210/jendso/bvad020; html:https://europepmc.org/articles/PMC9933896; pdf:https://europepmc.org/articles/PMC9933896?pdf=render 36240828,https://doi.org/10.1016/s2214-109x(22)00358-8,Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.,"Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, Xu XK, Chen D, Xiong J, Tae J, Tsang TK, Wu P, Lau EHY, Cowling BJ.",,The Lancet. Global health,2022,2022-11-01,Y,,,,"

Background

The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics.

Methods

For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect.

Findings

We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes.

Interpretation

Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community.

Funding

Health and Medical Research Fund, Hong Kong.",,doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849 -34095541,https://doi.org/10.23889/ijpds.v4i2.1134,A Profile of the SAIL Databank on the UK Secure Research Platform.,"Jones KH, Ford DV, Thompson S, Lyons RA.",,International journal of population data science,2019,2019-11-20,Y,,,,"

Background

The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.

Approach

SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.

Discussion

Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.

Conclusion

SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.",,doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render 34127232,https://doi.org/10.1016/j.artmed.2021.102083,Multi-domain clinical natural language processing with MedCAT: The Medical Concept Annotation Toolkit.,"Kraljevic Z, Searle T, Shek A, Roguski L, Noor K, Bean D, Mascio A, Zhu L, Folarin AA, Roberts A, Bendayan R, Richardson MP, Stewart R, Shah AD, Wong WK, Ibrahim Z, Teo JT, Dobson RJB.",,Artificial intelligence in medicine,2021,2021-05-01,N,Clinical Natural Language Processing; Clinical Concept Embeddings; Clinical Ontology Embeddings; Electronic Health Record Information Extraction,,,"Electronic health records (EHR) contain large volumes of unstructured text, requiring the application of information extraction (IE) technologies to enable clinical analysis. We present the open source Medical Concept Annotation Toolkit (MedCAT) that provides: (a) a novel self-supervised machine learning algorithm for extracting concepts using any concept vocabulary including UMLS/SNOMED-CT; (b) a feature-rich annotation interface for customizing and training IE models; and (c) integrations to the broader CogStack ecosystem for vendor-agnostic health system deployment. We show improved performance in extracting UMLS concepts from open datasets (F1:0.448-0.738 vs 0.429-0.650). Further real-world validation demonstrates SNOMED-CT extraction at 3 large London hospitals with self-supervised training over ∼8.8B words from ∼17M clinical records and further fine-tuning with ∼6K clinician annotated examples. We show strong transferability (F1 > 0.94) between hospitals, datasets and concept types indicating cross-domain EHR-agnostic utility for accelerated clinical and research use cases.",,doi:https://doi.org/10.1016/j.artmed.2021.102083 34390586,https://doi.org/10.1111/ejn.15423,Spectral clustering based on structural magnetic resonance imaging and its relationship with major depressive disorder and cognitive ability.,"Yeung HW, Shen X, Stolicyn A, de Nooij L, Harris MA, Romaniuk L, Buchanan CR, Waiter GD, Sandu AL, McNeil CJ, Murray A, Steele JD, Campbell A, Porteous D, Lawrie SM, McIntosh AM, Cox SR, Smith KM, Whalley HC.",,The European journal of neuroscience,2021,2021-09-02,N,Cognition; Clustering; Machine Learning; Major Depressive Disorder; Structural Neuroimaging; Markov Stability,,,"There is increasing interest in using data-driven unsupervised methods to identify structural underpinnings of common mental illnesses, including major depressive disorder (MDD) and associated traits such as cognition. However, studies are often limited to severe clinical cases with small sample sizes and most do not include replication. Here, we examine two relatively large samples with structural magnetic resonance imaging (MRI), measures of lifetime MDD and cognitive variables: Generation Scotland (GS subsample, N = 980) and UK Biobank (UKB, N = 8,900), for discovery and replication, using an exploratory approach. Regional measures of FreeSurfer derived cortical thickness (CT), cortical surface area (CSA), cortical volume (CV) and subcortical volume (subCV) were input into a clustering process, controlling for common covariates. The main analysis steps involved constructing participant K-nearest neighbour graphs and graph partitioning with Markov stability to determine optimal clustering of participants. Resultant clusters were (1) checked whether they were replicated in an independent cohort and (2) tested for associations with depression status and cognitive measures. Participants separated into two clusters based on structural brain measurements in GS subsample, with large Cohen's d effect sizes between clusters in higher order cortical regions, commonly associated with executive function and decision making. Clustering was replicated in the UKB sample, with high correlations of cluster effect sizes for CT, CSA, CV and subCV between cohorts across regions. The identified clusters were not significantly different with respect to MDD case-control status in either cohort (GS subsample: pFDR  = .2239-.6585; UKB: pFDR  = .2003-.7690). Significant differences in general cognitive ability were, however, found between the clusters for both datasets, for CSA, CV and subCV (GS subsample: d = 0.2529-.3490, pFDR  < .005; UKB: d = 0.0868-0.1070, pFDR  < .005). Our results suggest that there are replicable natural groupings of participants based on cortical and subcortical brain measures, which may be related to differences in cognitive performance, but not to the MDD case-control status.",,doi:https://doi.org/10.1111/ejn.15423 35842920,https://doi.org/10.1002/ehf2.14073,Blood-based biomarkers for the prediction of hypertrophic cardiomyopathy prognosis: a systematic review and meta-analysis. ,"Jansen M, Algül S, Bosman LP, Michels M, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,ESC heart failure,2022,2022-07-17,Y,,,,"Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease. HCM is an important cause of sudden cardiac death and may also lead to outflow tract obstruction and heart failure. Disease severity is highly variable and risk stratification remains limited. Therefore, we aimed to review current knowledge of prognostic blood-based biomarkers in HCM. A systematic literature search was performed on PubMed, Embase, and the Cochrane library to identify studies assessing plasma or serum biomarkers for outcomes involving malignant ventricular arrhythmia, outflow tract obstruction, and heart failure. Risk of bias was assessed using the QUIPS tool. Meta-analyses were performed using the random effects method. A total of 26 unique cohort studies assessing 42 biomarkers were identified. Overall risk of bias was moderate. Thirty-two biomarkers were significantly associated to an HCM outcome in at least one study (nine biomarkers in at least two studies). In pooled analyses, cardiovascular mortality was predicted by N-terminal prohormone of brain natriuretic peptide (hazard ratio [HR] 5.38 per log[pg/mL], 95% confidence interval [CI] 2.07-14.03, P < 0.001, I2  = 0%) and high-sensitivity C-reactive protein (HR 1.30 per μg/mL, 95% CI 1.00-1.68, P = 0.05, I2  = 78%), all-cause mortality by low-density lipoprotein cholesterol (HR 0.63 per μmol/mL, 95% CI 0.49-0.80, P < 0.001, I2  = 0%), and a combined congestive heart failure, malignant ventricular arrhythmia, and stroke outcome by high-sensitivity cardiac troponin T (pooled HR 4.19 for ≥0.014 ng/mL, 95% CI 2.22-7.88, P < 0.001, I2  = 0%). Quality of evidence was low-moderate. Several blood-based biomarkers were identified as predictors of HCM outcomes. Additional studies are required to validate their prognostic utility within current risk stratification models.",,doi:https://doi.org/10.1002/ehf2.14073; html:https://europepmc.org/articles/PMC9715795; pdf:https://europepmc.org/articles/PMC9715795?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14073 35953815,https://doi.org/10.1186/s12931-022-02130-6,Dynamic early warning scores for predicting clinical deterioration in patients with respiratory disease.,"Gonem S, Taylor A, Figueredo G, Forster S, Quinlan P, Garibaldi JM, McKeever TM, Shaw D.",,Respiratory research,2022,2022-08-11,Y,Risk Prediction; Clinical Deterioration; Early Warning Score,,,"

Background

The National Early Warning Score-2 (NEWS-2) is used to detect patient deterioration in UK hospitals but fails to take account of the detailed granularity or temporal trends in clinical observations. We used data-driven methods to develop dynamic early warning scores (DEWS) to address these deficiencies, and tested their accuracy in patients with respiratory disease for predicting (1) death or intensive care unit admission, occurring within 24 h (D/ICU), and (2) clinically significant deterioration requiring urgent intervention, occurring within 4 h (CSD).

Methods

Clinical observations data were extracted from electronic records for 31,590 respiratory in-patient episodes from April 2015 to December 2020 at a large acute NHS Trust. The timing of D/ICU was extracted for all episodes. 1100 in-patient episodes were annotated manually to record the timing of CSD, defined as a specific event requiring a change in treatment. Time series features were entered into logistic regression models to derive DEWS for each of the clinical outcomes. Area under the receiver operating characteristic curve (AUROC) was the primary measure of model accuracy.

Results

AUROC (95% confidence interval) for predicting D/ICU was 0.857 (0.852-0.862) for NEWS-2 and 0.906 (0.899-0.914) for DEWS in the validation data. AUROC for predicting CSD was 0.829 (0.817-0.842) for NEWS-2 and 0.877 (0.862-0.892) for DEWS. NEWS-2 ≥ 5 had sensitivity of 88.2% and specificity of 54.2% for predicting CSD, while DEWS ≥ 0.021 had higher sensitivity of 93.6% and approximately the same specificity of 54.3% for the same outcome. Using these cut-offs, 315 out of 347 (90.8%) CSD events were detected by both NEWS-2 and DEWS, at the time of the event or within the previous 4 h; 12 (3.5%) were detected by DEWS but not by NEWS-2, while 4 (1.2%) were detected by NEWS-2 but not by DEWS; 16 (4.6%) were not detected by either scoring system.

Conclusion

We have developed DEWS that display greater accuracy than NEWS-2 for predicting clinical deterioration events in patients with respiratory disease. Prospective validation studies are required to assess whether DEWS can be used to reduce missed deteriorations and false alarms in real-life clinical settings.",,doi:https://doi.org/10.1186/s12931-022-02130-6; html:https://europepmc.org/articles/PMC9367123; pdf:https://europepmc.org/articles/PMC9367123?pdf=render +34095541,https://doi.org/10.23889/ijpds.v4i2.1134,A Profile of the SAIL Databank on the UK Secure Research Platform.,"Jones KH, Ford DV, Thompson S, Lyons RA.",,International journal of population data science,2019,2019-11-20,Y,,,,"

Background

The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.

Approach

SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.

Discussion

Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.

Conclusion

SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.",,doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render 37278928,https://doi.org/10.1007/s12265-023-10398-2,Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.,"Jansen M, Schmidt AF, Jans JJM, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,Journal of cardiovascular translational research,2023,2023-06-06,N,Metabolism; Biomarker; hypertrophic cardiomyopathy; Acylcarnitine; Mybpc3,,,"Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.",,doi:https://doi.org/10.1007/s12265-023-10398-2 33500288,https://doi.org/10.1136/bmjopen-2020-042945,Hospital bed capacity and usage across secondary healthcare providers in England during the first wave of the COVID-19 pandemic: a descriptive analysis.,"Mateen BA, Wilde H, Dennis JM, Duncan A, Thomas N, McGovern A, Denaxas S, Keeling M, Vollmer S.",,BMJ open,2021,2021-01-26,Y,Public Health; Health Policy; Intensive & Critical Care; Covid-19,,,"

Objective

In this study, we describe the pattern of bed occupancy across England during the peak of the first wave of the COVID-19 pandemic.

Design

Descriptive survey.

Setting

All non-specialist secondary care providers in England from 27 March27to 5 June 2020.

Participants

Acute (non-specialist) trusts with a type 1 (ie, 24 hours/day, consultant-led) accident and emergency department (n=125), Nightingale (field) hospitals (n=7) and independent sector secondary care providers (n=195).

Main outcome measures

Two thresholds for 'safe occupancy' were used: 85% as per the Royal College of Emergency Medicine and 92% as per NHS Improvement.

Results

At peak availability, there were 2711 additional beds compatible with mechanical ventilation across England, reflecting a 53% increase in capacity, and occupancy never exceeded 62%. A consequence of the repurposing of beds meant that at the trough there were 8.7% (8508) fewer general and acute beds across England, but occupancy never exceeded 72%. The closest to full occupancy of general and acute bed (surge) capacity that any trust in England reached was 99.8% . For beds compatible with mechanical ventilation there were 326 trust-days (3.7%) spent above 85% of surge capacity and 154 trust-days (1.8%) spent above 92%. 23 trusts spent a cumulative 81 days at 100% saturation of their surge ventilator bed capacity (median number of days per trust=1, range: 1-17). However, only three sustainability and transformation partnerships (aggregates of geographically co-located trusts) reached 100% saturation of their mechanical ventilation beds.

Conclusions

Throughout the first wave of the pandemic, an adequate supply of all bed types existed at a national level. However, due to an unequal distribution of bed utilisation, many trusts spent a significant period operating above 'safe-occupancy' thresholds despite substantial capacity in geographically co-located trusts, a key operational issue to address in preparing for future waves.",,doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?pdf=render 33632741,https://doi.org/10.2337/db20-0895,"Relationship Between Glycemia and Cognitive Function, Structural Brain Outcomes, and Dementia: A Mendelian Randomization Study in the UK Biobank.","Garfield V, Farmaki AE, Fatemifar G, Eastwood SV, Mathur R, Rentsch CT, Denaxas S, Bhaskaran K, Smeeth L, Chaturvedi N.",,Diabetes,2021,2021-02-25,N,,,,"We investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank (n = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA1c (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal volume (HV), white matter hyperintensity volume (WMHV), and Alzheimer dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and diabetes and HbA1c We used conventional inverse-variance-weighted (IVW) MR alongside MR sensitivity analyses. Using IVW, genetic liability to type 2 diabetes was not associated with RT (exponentiated β [expβ] = 1.00 [95% CI 1.00; 1.00]), visual memory (expβ = 1.00 [95% CI 0.99; 1.00]), WMHV (expβ = 0.99 [95% CI 0.97; 1.01]), HV (β-coefficient mm3 = -2.30 [95% CI -12.39; 7.78]) or AD (odds ratio [OR] 1.15 [95% CI 0.87; 1.52]). HbA1c was not associated with RT (expβ = 1.00 [95% CI 0.99; 1.02]), visual memory (expβ = 0.99 [95% CI 0.96; 1.02]), WMHV (expβ = 1.03 [95% CI 0.88; 1.22]), HV (β = -21.31 [95% CI -82.96; 40.34]), or risk of AD (OR 1.09 [95% CI 0.42; 2.83]). IVW showed that reaction time was not associated with diabetes risk (OR 0.94 [95% CI 0.54; 1.65]), or with HbA1c (β-coefficient mmol/mol = -0.88 [95% CI = -1.88; 0.13]) after exclusion of a pleiotropic variant. Overall, we observed little evidence of causal association between genetic instruments for type 2 diabetes or peripheral glycemia and some measures of cognition and brain structure in midlife.",,doi:https://doi.org/10.2337/db20-0895 @@ -1192,13 +1195,13 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33144367,https://doi.org/10.3399/bjgpopen20x101109,Evaluating a cardiovascular disease risk management care continuum within a learning healthcare system: a prospective cohort study. ,"Groenhof TKJ, Lely AT, Haitjema S, Nathoe HM, Kortekaas MF, Asselbergs FW, Bots ML, Hollander M, UCC CVRM study group.",,BJGP open,2020,2020-12-15,Y,,,,"Many patients now present with multimorbidity and chronicity of disease. This means that multidisciplinary management in a care continuum, integrating primary care and hospital care services, is needed to ensure high quality care. To evaluate cardiovascular risk management (CVRM) via linkage of health data sources, as an example of a multidisciplinary continuum within a learning healthcare system (LHS). In this prospective cohort study, data were linked from the Utrecht Cardiovascular Cohort (UCC) to the Julius General Practitioners' Network (JGPN) database. UCC offers structured CVRM at referral to the University Medical Centre (UMC) Utrecht. JGPN consists of electronic health record (EHR) data from referring GPs. The cardiovascular risk factors were extracted for each patient 13 months before referral (JGPN), at UCC inclusion, and during 12 months follow-up (JGPN). The following areas were assessed: registration of risk factors; detection of risk factor(s) requiring treatment at UCC; communication of risk factors and actionable suggestions from the specialist to the GP; and change of management during follow-up. In 52% of patients, ≥1 risk factors were registered (that is, extractable from structured fields within routine care health records) before UCC. In 12%-72% of patients, risk factor(s) existed that required (change or start of) treatment at UCC inclusion. Specialist communication included the complete risk profile in 67% of letters, but lacked actionable suggestions in 86%. In 29% of patients, at least one risk factor was registered after UCC. Change in management in GP records was seen in 21%-58% of them. Evaluation of a multidisciplinary LHS is possible via linkage of health data sources. Efforts have to be made to improve registration in primary care, as well as communication on findings and actionable suggestions for follow-up to bridge the gap in the CVRM continuum.",,doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render 33866023,https://doi.org/10.1016/j.oret.2021.04.001,Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.,"Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.",,Ophthalmology. Retina,2021,2021-04-16,N,AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study,,,"

Purpose

Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.

Design

Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.

Participants

Treatment-naïve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.

Methods

Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December 2018.

Main outcome measures

Visual acuity (VA), number of injections, and number of visits.

Results

A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.

Conclusions

Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.",,doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001 32838035,https://doi.org/10.1002/lrh2.10236,Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.,"Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",,Learning health systems,2021,2020-07-14,Y,Artificial intelligence; Covid‐19; Rapid Learning Systems,,,"

Introduction

We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.

Methods

The PROforma guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.

Results

PROforma and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.

Conclusions

This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",,doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render -36752447,https://doi.org/10.1016/j.jcmg.2022.11.012,Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.,"Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.",,JACC. Cardiovascular imaging,2023,2023-01-11,N,Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement,,,"

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.",,doi:https://doi.org/10.1016/j.jcmg.2022.11.012 35692035,https://doi.org/10.1186/s12916-022-02399-w,"Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.","Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,BMC medicine,2022,2022-06-13,Y,Fatty acids; Cardiovascular diseases; Mendelian Randomization,,,"

Background

Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

Methods

We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

Results

GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

Conclusions

We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.",,doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render -36228971,https://doi.org/10.1016/j.jclinepi.2022.10.011,"In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.","Nichols L, Taverner T, Crowe F, Richardson S, Yau C, Kiddle S, Kirk P, Barrett J, Nirantharakumar K, Griffin S, Edwards D, Marshall T.",,Journal of clinical epidemiology,2022,2022-10-11,Y,Hierarchical cluster analysis; Clustering Methods; Latent Class Analysis; Electronic Medical Records; Multimorbidity; K-means; Multiple Correspondence Analysis,,,"

Background and objectives

To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering.

Methods

We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples.

Results

In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54).

Conclusion

LCA achieved higher aRI than other clustering algorithms.",,doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render +36752447,https://doi.org/10.1016/j.jcmg.2022.11.012,Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.,"Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.",,JACC. Cardiovascular imaging,2023,2023-01-11,N,Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement,,,"

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.",,doi:https://doi.org/10.1016/j.jcmg.2022.11.012 31361079,https://doi.org/10.1111/1742-6723.13361,"Animal-vehicle collisions in Victoria, Australia: An under-recognised cause of road traffic crashes.","Ang JY, Gabbe B, Cameron P, Beck B.",,Emergency medicine Australasia : EMA,2019,2019-07-30,N,Injury; Prevention; Traffic; Motor Vehicle,,,"

Objective

Non-fatal injuries sustained from animal-vehicle collisions are a globally under-recognised road safety issue, with limited data on these crash types. The present study aimed to quantify the number and causes of major trauma events resulting from animal-vehicle collisions.

Methods

The study was a retrospective analysis of major trauma cases occurring in Victoria, Australia, between 2007 and 2016, using data from the population-based Victorian State Trauma Registry. To identify animal-vehicle collisions, Victorian State Trauma Registry injury codes were combined with text-mining of the text description of the injury event.

Results

Over the 10 year period, there were 152 major trauma patients who were admitted to Victorian trauma-receiving hospitals due to vehicle collisions with animals. The crude population-based incidence rate for animal-vehicle collisions increased by 6.7% per year (incidence rate ratio 1.07; 95% confidence interval 1.01-1.13; P = 0.02).

Conclusion

Development of systematic recording methods of animal-vehicle collisions will improve reporting of these crash types to assist future studies in implementing effective countermeasures.",,doi:https://doi.org/10.1111/1742-6723.13361 +36228971,https://doi.org/10.1016/j.jclinepi.2022.10.011,"In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.","Nichols L, Taverner T, Crowe F, Richardson S, Yau C, Kiddle S, Kirk P, Barrett J, Nirantharakumar K, Griffin S, Edwards D, Marshall T.",,Journal of clinical epidemiology,2022,2022-10-11,Y,Hierarchical cluster analysis; Clustering Methods; Latent Class Analysis; Electronic Medical Records; Multimorbidity; K-means; Multiple Correspondence Analysis,,,"

Background and objectives

To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering.

Methods

We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples.

Results

In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54).

Conclusion

LCA achieved higher aRI than other clustering algorithms.",,doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render 35351727,https://doi.org/10.1136/bmjopen-2021-057909,Impact of chronic kidney disease on case ascertainment for hospitalised acute myocardial infarction: an English cohort study.,"Bidulka P, Scott J, Taylor DM, Udayaraj U, Caskey F, Teece L, Sweeting M, Deanfield J, de Belder M, Denaxas S, Weston C, Adlam D, Nitsch D.",,BMJ open,2022,2022-03-28,Y,Myocardial infarction; Cardiology; Nephrology; Audit; Statistics & Research Methods,,,"

Objectives

Acute myocardial infarction (AMI) case ascertainment improves for the UK general population using linked health data sets. Because care pathways for people with chronic kidney disease (CKD) change based on disease severity, AMI case ascertainment for these people may differ compared with the general population. We aimed to determine the association between CKD severity and AMI case ascertainment in two secondary care data sets, and the agreement in estimated glomerular filtration rate (eGFR) between the same data sets.

Methods

We used a cohort study design. Primary care records for people with CKD or risk factors for CKD, identified using the National CKD Audit (2015-2017), were linked to the Myocardial Ischaemia National Audit Project (MINAP, 2007-2017) and Hospital Episode Statistics (HES, 2007-2017) secondary care registries. People with an AMI recorded in either MINAP, HES or both were included in the study cohort. CKD status was defined using eGFR, derived from the most recent serum creatinine value recorded in primary care. Moderate-severe CKD was defined as eGFR <60 mL/min/1.73 m2, and mild CKD or at risk of CKD was defined as eGFR ≥60 mL/min/1.73 m2 or eGFR missing. CKD stages were grouped as (1) At risk of CKD and Stages 1-2 (eGFR missing or ≥60 mL/min/1.73 m2), (2) Stage 3a (eGFR 45-59 mL/min/1.73 m2), (3) Stage 3b (eGFR 30-44 mL/min/1.73 m2) and (4) Stages 4-5 (eGFR <30 mL/min/1.73 m2).

Results

We identified 6748 AMIs: 23% were recorded in both MINAP and HES, 66% in HES only and 11% in MINAP only. Compared with people at risk of CKD or with mild CKD, AMIs in people with moderate-severe CKD were more likely to be recorded in both MINAP and HES (42% vs 11%, respectively), or MINAP only (22% vs 5%), and less likely to be recorded in HES only (36% vs 84%). People with AMIs recorded in HES only or MINAP only had increased odds of death during hospitalisation compared with those recorded in both (adjusted OR 1.61, 95% CI 1.32 to 1.96 and OR 1.60, 95% CI 1.26 to 2.04, respectively). Agreement between eGFR at AMI admission (MINAP) and in primary care was poor (kappa (K) 0.42, SE 0.012).

Conclusions

AMI case ascertainment is incomplete in both MINAP and HES, and is associated with CKD severity.",,doi:https://doi.org/10.1136/bmjopen-2021-057909; html:https://europepmc.org/articles/PMC8961119; pdf:https://europepmc.org/articles/PMC8961119?pdf=render -35916366,https://doi.org/10.7554/elife.76272,Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.,"Lemmelä S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",,eLife,2022,2022-08-02,Y,Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation,,,"Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",,doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render 31345952,https://doi.org/10.1136/heartjnl-2018-313855,Do beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve outcomes in patients with heart failure and left ventricular ejection fraction >40%?,"Lumbers RT, Martin N, Manoharan K, Thomas J, Davies LC.",,Heart (British Cardiac Society),2019,2019-07-25,N,Pharmacology; Meta-analysis; epidemiology; Heart Failure With Preserved Ejection Fraction; Systemic Review,,,,,doi:https://doi.org/10.1136/heartjnl-2018-313855 +35916366,https://doi.org/10.7554/elife.76272,Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.,"Lemmelä S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",,eLife,2022,2022-08-02,Y,Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation,,,"Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",,doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render 30972781,https://doi.org/10.1111/apt.15232,Early and late mortality following unscheduled admissions for severe liver disease across England and Wales.,"Roberts SE, John A, Brown J, Napier DJ, Lyons RA, Williams JG.",,Alimentary pharmacology & therapeutics,2019,2019-04-11,Y,,,,"

Background

There is a known shortfall in hepatology service resources across England and Wales.

Aim

To investigate early and late mortality following unscheduled admissions for severe liver disease, overall and by cause of death, and to determine how mortality is related to admissions to transplant centres, transplant surgery, hospital size, consultant specialty, patient socio-demographics, seasonal and geographical factors.

Methods

Cohorts of people with a first unscheduled admission for severe liver disease across England and Wales from 2004, based on record linkage of national inpatient and mortality data.

Findings

Mortality for alcoholic liver disease and hepatic failure was 23.4% and 35.4% respectively at 60 days and 61.8% and 57.1% at 5 years. Standardised mortality ratios (SMRs) were extremely high at 60 days (184 and 117 respectively) and remained highly increased at 5 years (16.7 and 6.3). Mortality at 5 years was most elevated from liver disease, viral hepatitis and varices. The 60-day mortality was significantly lower for patients seen by consultant hepatologists and gastroenterologists. Both early and late mortality were significantly reduced for patients admitted to transplant centres or larger hospitals, who received a liver transplant, or were resident in London. Early mortality was significantly higher for patients admitted in winter and autumn, while elevated mortality among the most vs least deprived quintile increased with longer follow-up.

Conclusions

The study shows a very poor prognosis for people with unscheduled hospitalisation for severe liver disease. The findings suggest that access to specialist expertise and services improves survival, both in the short and long term.",,doi:https://doi.org/10.1111/apt.15232; html:https://europepmc.org/articles/PMC6519290; pdf:https://europepmc.org/articles/PMC6519290?pdf=render 31822919,https://doi.org/10.1093/pubmed/fdz172,"Unmet needs of women with GDM: a health needs assessment in Sandwell, West Midlands.","Plant N, Šumilo D, Chapman R, Webber J, Saravanan P, Nirantharakumar K.",,"Journal of public health (Oxford, England)",2020,2020-11-01,N,United Kingdom; Needs Assessment; Gestational Diabetes,,,"

Background

Gestational diabetes mellitus (GDM) affects over 4% of pregnancies in England. We investigated GDM epidemiology within ethnically diverse population and the current offer of services to women with previous GDM to reduce their type 2 diabetes mellitus (T2DM) risk.

Methods

(i) Analysis of routinely collected maternity data examining GDM incidence and risk factors; (ii) local authority self-assessment questionnaire on public health interventions targeting women with previous GDM and (iii) service development discussions regarding the current pathway and areas for improvement.

Results

Of 9390 births between 2014 and 2018, 6.8% had a record of GDM. High body mass index (BMI), maternal age, and ethnicity (South Asian and some mixed ethnic backgrounds) were independent predictors of GDM. There were no public health commissioned services specifically targeting women with previous GDM. Weaknesses in transition from secondary to primary care and areas for improvement when screening for GDM were identified.

Conclusions

GDM burden in this population was high. Awareness should be raised on the importance of regular glucose testing and lifestyle modification to delay or prevent progression to T2DM, particularly within high risk groups. The potential for health visitors to contribute to this should be explored. Commissioners should review evidence to develop a flexible lifestyle services model to meet the specific needs of these women.",,doi:https://doi.org/10.1093/pubmed/fdz172 35802687,https://doi.org/10.1371/journal.pone.0270668,"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.","Godolphin PJ, Fisher DJ, Berry LR, Derde LPG, Diaz JV, Gordon AC, Lorenzi E, Marshall JC, Murthy S, Shankar-Hari M, Sterne JAC, Tierney JF, Vale CL.",,PloS one,2022,2022-07-08,Y,,,,"

Background

A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.

Methods

Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.

Findings

One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.

Conclusions

Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.",,doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable @@ -1217,8 +1220,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 35089054,https://doi.org/10.1161/circep.121.010221,Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy.,"Bosman LP, Wang W, Lie ØH, van Lint FHM, Rootwelt-Norberg C, Murray B, Tichnell C, Cadrin-Tourigny J, van Tintelen JP, Asselbergs FW, Calkins H, Te Riele ASJM, Haugaa KH, James CA.",,Circulation. Arrhythmia and electrophysiology,2022,2022-01-28,N,Prognosis; Exercise; Arrhythmogenic right ventricular dysplasia,,,"

Background

Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (arvcrisk.com). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise.

Methods

We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models.

Results

We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7-9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53-2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71-0.84) and showed no significant improvement (Akaike information criterion change, <2).

Conclusions

Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification.",,doi:https://doi.org/10.1161/CIRCEP.121.010221 31500613,https://doi.org/10.1186/s12911-019-0908-7,A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records.,"Wheater E, Mair G, Sudlow C, Alex B, Grover C, Whiteley W.",,BMC medical informatics and decision making,2019,2019-09-09,Y,Stroke; Phenotyping; Brain imaging; Radiology; Natural Language Processing; Radiology Reports,"Applied Analytics, Better Care",,"

Background

Manual coding of phenotypes in brain radiology reports is time consuming. We developed a natural language processing (NLP) algorithm to enable automatic identification of brain imaging in radiology reports performed in routine clinical practice in the UK National Health Service (NHS).

Methods

We used anonymized text brain imaging reports from a cohort study of stroke/TIA patients and from a regional hospital to develop and test an NLP algorithm. Two experts marked up text in 1692 reports for 24 cerebrovascular and other neurological phenotypes. We developed and tested a rule-based NLP algorithm first within the cohort study, and further evaluated it in the reports from the regional hospital.

Results

The agreement between expert readers was excellent (Cohen's κ =0.93) in both datasets. In the final test dataset (n = 700) in unseen regional hospital reports, the algorithm had very good performance for a report of any ischaemic stroke [sensitivity 89% (95% CI:81-94); positive predictive value (PPV) 85% (76-90); specificity 100% (95% CI:0.99-1.00)]; any haemorrhagic stroke [sensitivity 96% (95% CI: 80-99), PPV 72% (95% CI:55-84); specificity 100% (95% CI:0.99-1.00)]; brain tumours [sensitivity 96% (CI:87-99); PPV 84% (73-91); specificity: 100% (95% CI:0.99-1.00)] and cerebral small vessel disease and cerebral atrophy (sensitivity, PPV and specificity all > 97%). We obtained few reports of subarachnoid haemorrhage, microbleeds or subdural haematomas. In 110,695 reports from NHS Tayside, atrophy (n = 28,757, 26%), small vessel disease (15,015, 14%) and old, deep ischaemic strokes (10,636, 10%) were the commonest findings.

Conclusions

An NLP algorithm can be developed in UK NHS radiology records to allow identification of cohorts of patients with important brain imaging phenotypes at a scale that would otherwise not be possible.",,doi:https://doi.org/10.1186/s12911-019-0908-7; html:https://europepmc.org/articles/PMC6734359; pdf:https://europepmc.org/articles/PMC6734359?pdf=render 32524641,https://doi.org/10.1002/sim.8556,Selective recruitment designs for improving observational studies using electronic health records.,"Barrett JE, Cakiroglu A, Bunce C, Shah A, Denaxas S.",,Statistics in medicine,2020,2020-06-10,Y,Electronic Health Records; Observational Study; Optimal Experimental Design; Selective Recruitment,,,"Large-scale electronic health records (EHRs) present an opportunity to quickly identify suitable individuals in order to directly invite them to participate in an observational study. EHRs can contain data from millions of individuals, raising the question of how to optimally select a cohort of size n from a larger pool of size N. In this article, we propose a simple selective recruitment protocol that selects a cohort in which covariates of interest tend to have a uniform distribution. We show that selectively recruited cohorts potentially offer greater statistical power and more accurate parameter estimates than randomly selected cohorts. Our protocol can be applied to studies with multiple categorical and continuous covariates. We apply our protocol to a numerically simulated prospective observational study using an EHR database of stable acute coronary disease patients from 82 089 individuals in the U.K. Selective recruitment designs require a smaller sample size, leading to more efficient and cost-effective studies.",,doi:https://doi.org/10.1002/sim.8556; html:https://europepmc.org/articles/PMC8432147; pdf:https://europepmc.org/articles/PMC8432147?pdf=render -35072885,https://doi.org/10.1007/s10439-022-02905-4,Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.,"Boonstra MJ, Roudijk RW, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, Loh P, van Dam PM.",,Annals of biomedical engineering,2022,2022-01-24,Y,Electrophysiology; Electrocardiography; Cardiovascular Imaging; Electrocardiographic Imaging; Electro-anatomical Mapping; His-purkinje System; Inverse Electrocardiography; Equivalent Dipole Layer; Non-invasive Cardiac Activation Mapping,,,"Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.",,doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render 34769922,https://doi.org/10.3390/ijerph182111380,"Driver, Collision and Meteorological Characteristics of Motor Vehicle Collisions among Road Trauma Survivors. ","Giummarra MJ, Xu R, Guo Y, Dipnall JF, Ponsford J, Cameron PA, Ameratunga S, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-10-29,Y,,,,"Road trauma remains a significant public health problem. We aimed to identify sub-groups of motor vehicle collisions in Victoria, Australia, and the association between collision characteristics and outcomes up to 24 months post-injury. Data were extracted from the Victorian State Trauma Registry for injured drivers aged ≥16 years, from 2010 to 2016, with a compensation claim who survived ≥12 months post-injury. People with intentional or severe head injury were excluded, resulting in 2735 cases. Latent class analysis was used to identify collision classes for driver fault and blood alcohol concentration (BAC), day and time of collision, weather conditions, single vs. multi-vehicle and regional vs. metropolitan injury location. Five classes were identified: (1) daytime multi-vehicle collisions, no other at fault; (2) daytime single-vehicle predominantly weekday collisions; (3) evening single-vehicle collisions, no other at fault, 36% with BAC ≥ 0.05; (4) sunrise or sunset weekday collisions; and (5) dusk and evening multi-vehicle in metropolitan areas with BAC < 0.05. Mixed linear and logistic regression analyses examined associations between collision class and return to work, health (EQ-5D-3L summary score) and independent function Glasgow Outcome Scale - Extended at 6, 12 and 24 months. After adjusting for demographic, health and injury characteristics, collision class was not associated with outcomes. Rather, risk of poor outcomes was associated with age, sex and socioeconomic disadvantage, education, pre-injury health and injury severity. People at risk of poor recovery may be identified from factors available during the hospital admission and may benefit from clinical assessment and targeted referrals and treatments.",,doi:https://doi.org/10.3390/ijerph182111380; html:https://europepmc.org/articles/PMC8583338; pdf:https://europepmc.org/articles/PMC8583338?pdf=render +35072885,https://doi.org/10.1007/s10439-022-02905-4,Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.,"Boonstra MJ, Roudijk RW, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, Loh P, van Dam PM.",,Annals of biomedical engineering,2022,2022-01-24,Y,Electrophysiology; Electrocardiography; Cardiovascular Imaging; Electrocardiographic Imaging; Electro-anatomical Mapping; His-purkinje System; Inverse Electrocardiography; Equivalent Dipole Layer; Non-invasive Cardiac Activation Mapping,,,"Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.",,doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render 33719753,https://doi.org/10.1080/13607863.2021.1893270,Cognition in informal caregivers: evidence from an English population study.,"García-Castro FJ, Bendayan R, Dobson RJB, Blanca MJ.",,Aging & mental health,2022,2021-03-14,N,Older Adults; Executive Function; Verbal Memory; Caregiving Duration,,,"

Background and objectives

The relationship between caregiving and cognition remains unclear. We investigate this association comparing four cognitive tasks and exploring the role of potential explanatory pathways such as healthy behaviours (healthy caregiver hypothesis) and depression (stress process model).

Research design and methods

Respondents were from English Longitudinal Study of Ageing (ELSA) (N = 8910). Cognitive tasks included immediate and delayed word recall, verbal fluency and serial 7 subtraction. Series of hierarchical linear regressions were performed. Adjustments included socio-demographics, health related variables, health behaviours and depression.

Results

Being a caregiver was positively associated with immediate and delayed recall, verbal fluency but not with serial 7. For immediate and delayed recall, these associations were partially attenuated when adjusting for health behaviours, and depression. For verbal fluency, associations were partially attenuated when adjusting for depression but fully attenuated when adjusting for health behaviours. No associations were found for serial 7.

Discussion and implications

Our findings show that caregivers have higher level of memory and executive function compared to non-caregivers. For memory, we found that although health behaviours and depression can have a role in this association, they do not fully explain it. However, health behaviours seem to have a clear role in the association with executive function. Public health and policy do not need to target specifically cognitive function but other areas as the promotion of healthy behaviours and psychological adjustment such as preventing depression and promoting physical activity in caregivers.",,doi:https://doi.org/10.1080/13607863.2021.1893270 36054463,https://doi.org/10.1111/ans.17985,Examining the patient profile and variance of management and in-hospital outcomes for Australian adult burns patients.,"Tracy LM, Darton A, Gabbe BJ, Heath K, Kurmis R, Lisec C, Lo C, Singer Y, Wood FM, Cleland HJ.",,ANZ journal of surgery,2022,2022-08-22,Y,Adult; Variation; Australia; Burn; Registry,,,"

Background

Burn injuries are a common subtype of trauma. Variation in models of care impacts clinical measures of interest, but a nation-wide examination of these measures has not been undertaken. Using data from the Burns Registry of Australia and New Zealand (BRANZ), we explored variation between Australian adult burn services with respect to treatment and clinical measures of interest.

Methods

Data for admissions July 2016 to June 2020 were extracted. Clinical measures of interest included intensive care admission, skin grafting, in-hospital death, unplanned readmissions, and length of stay (LOS). Estimated probabilities, means, and corresponding 95% confidence intervals (CI) were calculated for each service.

Results

The BRANZ recorded 8365 admissions during the study period. Variation between specialist burn services in admissions, demographics, management, and clinical measures of interest were observed. This variation remained after accounting for covariates. Specifically, the adjusted proportion (95% CI) of in-hospital mortality ranged from 0.15% (0.10-0.21%) to 1.22% (0.9-1.5%). The adjusted mean LOS ranged from 3.8 (3.3-4.3) to 8.2 (6.7-9.7) days.

Conclusions

A decade after its launch, BRANZ data displays variation between Australian specialist burn services. We suspect differences in models of care between services contributes to this variation. Ongoing research has begun to explore reasons underlying how this variation influences clinical measures of interest. Further engagement with services about models of care will enhance understanding of this variation and develop evidence-based guidelines for burn care in Australia.",,doi:https://doi.org/10.1111/ans.17985; html:https://europepmc.org/articles/PMC9804322; pdf:https://europepmc.org/articles/PMC9804322?pdf=render 34870256,https://doi.org/10.1016/j.lanepe.2021.100267,Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.,"Liu Y, Sandmann FG, Barnard RC, Pearson CAB, Pastore R, Pebody R, Flasche S, Jit M.",,The Lancet regional health. Europe,2022,2021-11-30,Y,Europe; Health Economics; Mathematical Modelling; Policy Evaluation; Vaccine Policy; Multicountry Analysis; Covid-19,,,"

Background

Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region.

Methods

We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection.

Findings

Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable.

Interpretation

The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults.

Funding

World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust.",,doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render @@ -1230,8 +1233,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33053479,https://doi.org/10.1016/j.chiabu.2020.104760,Characterizing newborn and older infant entries into care in England between 2006 and 2014.,"Pearson RJ, Jay MA, O'Donnell M, Wijlaars L, Gilbert R.",,Child abuse & neglect,2020,2020-10-11,Y,Longitudinal data; Infancy; Latent Class Analysis; Entry Into Care; Out-of-court Arrangements,,,"

Background

The risk of entry to state care during infancy is increasing, both here in England and abroad, with most entering within a week of birth ('newborns'). However, little is known about these infants or of their pathways through care over early childhood.

Objective

To characterize infant entries to care in England.

Participants and setting

All children in England who first entered care during infancy, between April 2006 and March 2014 (n = 42,000).

Methods

We compared sociodemographic and care characteristics for infants entering care over the study period by age at first entry (newborn: <1wks, older infant 1-51wks). Among those who entered before April 2010, we further characterized care over follow-up (i.e. 4 years from first entry) and employed latent class analysis to uncover any common pathways through care.

Results

Almost 40 % of infants first entered care as a newborn. Most infants first entered care under s 20 arrangements (i.e. out-of-court, 60 % of newborns vs 47 % of older infants). Among infants entering before April 2010, most were adopted over follow-up (60 % vs 37 %), though many were restored to parental care (20 % vs 32 %) or exited care to live with extended family (13 % vs 19 %). One in six infants (17.7 %) had particularly unstable care trajectories over early childhood, typified by three or more placements or failed reunification.

Conclusions

Evidence-based strengthening of pre-birth social work support is needed to improve preventive interventions before birth, to more effectively target infant placement into care. Linkages between child protection records and information on parents are needed to inform preventive strategies.",,doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112 34364665,https://doi.org/10.1016/j.cardfail.2021.05.012,Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.,"Savarese G, Uijl A, Lund LH, Anker SD, Asselbergs F, Fitchett D, Inzucchi SE, Koudstaal S, Ofstad AP, Schrage B, Vedin O, Wanner C, Zannad F, Zwiener I, Butler J.",,Journal of cardiac failure,2021,2021-08-01,N,Type 2 diabetes mellitus; Heart Failure With Preserved Ejection Fraction; Heart Failure With Reduced Ejection Fraction; Empagliflozin; Empa-reg Outcome; Heart Failure With Mid-range Ejection Fraction; Heart Failure With Mildly Reduced Ejection Fraction,,,"

Background

In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.

Methods and results

We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31-1.17], 0.79 [0.51-1.23], and 0.63 [0.50-0.78], respectively; P interaction = 0.62).

Conclusions

In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.",,doi:https://doi.org/10.1016/j.cardfail.2021.05.012 34095527,https://doi.org/10.23889/ijpds.v4i1.581,Electronic Longitudinal Alcohol Study in Communities (ELAStiC) Wales - protocol for platform development.,"Trefan L, Akbari A, Paranjothy S, Farewell DM, Gartner A, Fone D, Greene J, Evans A, Smith A, Adekanmbi V, Kennedy J, Lyons RA, Moore SC.",,International journal of population data science,2019,2019-05-20,Y,,,,"

Introduction

Excessive alcohol consumption has adverse effects on health and there is a recognised need for the longitudinal analysis of population data to improve our understanding of the patterns of alcohol use, harms to consumers and those in their immediate environment. The UK has a number of linkable, longitudinal databases that if assembled properly could support valuable research on this topic.

Aims and objectives

This paper describes the development of a broad set of cross-linked cohorts, e-cohorts, surveys and linked electronic healthcare records (EHRs) to construct an alcohol-specific analytical platform in the United Kingdom using datasets on the population of Wales.The objective of this paper is to provide a description of existing key datasets integrated with existing, routinely collected electronic health data on a secure platform, and relevant derived variables to enable population-based research on alcohol-related harm in Wales. We illustrate our use of these data with some exemplar research questions that are currently under investigation.

Methods

Record-linkage of routine and observational datasets. Routine data includes hospital admissions, general practice, and cohorts specific to children. Two observational studies were included. Routine socioeconomic descriptors and mortality data were also linked.

Conclusion

We described a record-linked, population-based research protocol for alcohol related harm on a secure platform. As the datasets used here are available in many countries, ELAStiC provides a template for setting up similar initiatives in other countries. We have also defined a number of alcohol specific variables using routinely-collected available data that can be used in other epidemiological studies into alcohol related outcomes. With over 10 years of longitudinal data, it will help to understand alcohol-related disease and health trajectories across the lifespan.",,doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render -36958365,https://doi.org/10.1016/s2352-3018(23)00028-0,Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.,"Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.",,The lancet. HIV,2023,2023-03-20,N,,,,"

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0 34429368,https://doi.org/10.1136/heartjnl-2021-319566,Sex disparity in subsequent outcomes in survivors of coronary heart disease.,"Akyea RK, Kontopantelis E, Kai J, Weng SF, Patel RS, Asselbergs FW, Qureshi N.",,Heart (British Cardiac Society),2022,2021-08-24,N,Sex difference; Coronary Heart Disease; Secondary Prevention; Competing Risks; Major Adverse Cardiovascular Events,,,"

Objective

Evidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.

Methods

Using a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.

Results

There were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).

Conclusions

After incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.",,doi:https://doi.org/10.1136/heartjnl-2021-319566 +36958365,https://doi.org/10.1016/s2352-3018(23)00028-0,Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.,"Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.",,The lancet. HIV,2023,2023-03-20,N,,,,"

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0 36944376,https://doi.org/10.1098/rsob.220373,"The lipid linked oligosaccharide polymerase Wzy and its regulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex.","Weckener M, Woodward LS, Clarke BR, Liu H, Ward PN, Le Bas A, Bhella D, Whitfield C, Naismith JH.",,Open biology,2023,2023-03-22,Y,Oligosaccharides; Lipid; Regulating; Polymerase; Wzy,,,"The enterobacterial common antigen (ECA) is a carbohydrate polymer that is associated with the cell envelope in the Enterobacteriaceae. ECA contains a repeating trisaccharide which is polymerized by WzyE, a member of the Wzy membrane protein polymerase superfamily. WzyE activity is regulated by a membrane protein polysaccharide co-polymerase, WzzE. Förster resonance energy transfer experiments demonstrate that WzyE and WzzE from Pectobacterium atrosepticum form a complex in vivo, and immunoblotting and cryo-electron microscopy (cryo-EM) analysis confirm a defined stoichiometry of approximately eight WzzE to one WzyE. Low-resolution cryo-EM reconstructions of the complex, aided by an antibody recognizing the C-terminus of WzyE, reveals WzyE sits in the central membrane lumen formed by the octameric arrangement of the transmembrane helices of WzzE. The pairing of Wzy and Wzz is found in polymerization systems for other bacterial polymers, including lipopolysaccharide O-antigens and capsular polysaccharides. The data provide new structural insight into a conserved mechanism for regulating polysaccharide chain length in bacteria.",,doi:https://doi.org/10.1098/rsob.220373; html:https://europepmc.org/articles/PMC10030265; pdf:https://europepmc.org/articles/PMC10030265?pdf=render 35922433,https://doi.org/10.1038/s41467-022-32219-x,Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.,"Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, Bülow R, Völker U, Völzke H, Dörr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",,Nature communications,2022,2022-08-03,Y,,,,"Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",,doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render @@ -1241,15 +1244,15 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 36774358,https://doi.org/10.1038/s41467-023-36439-7,Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer. ,"Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.",,Nature communications,2023,2023-02-11,Y,,,,"The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.",,doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render 33939952,https://doi.org/10.1016/s0140-6736(21)00949-1,COVID-19 and disparities affecting ethnic minorities.,"Morales DR, Ali SN.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,,,doi:https://doi.org/10.1016/S0140-6736(21)00949-1; html:https://europepmc.org/articles/PMC9755653; pdf:https://europepmc.org/articles/PMC9755653?pdf=render 32579178,https://doi.org/10.1001/jamadermatol.2020.1948,Association Between Atopic Eczema and Cancer in England and Denmark.,"Mansfield KE, Schmidt SAJ, Darvalics B, Mulick A, Abuabara K, Wong AYS, Sørensen HT, Smeeth L, Bhaskaran K, Dos Santos Silva I, Silverwood RJ, Langan SM.",,JAMA dermatology,2020,2020-10-01,Y,,,,"

Importance

Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk.

Objective

To investigate whether atopic eczema is associated with cancer.

Design, setting, and participants

Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema.

Exposure

Atopic eczema.

Main outcomes and measures

Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema.

Results

In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide.

Conclusions and relevance

The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.",,doi:https://doi.org/10.1001/jamadermatol.2020.1948; html:https://europepmc.org/articles/PMC7315391 -36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render +36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf 35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render 30745170,https://doi.org/10.1016/j.ebiom.2019.02.005,"Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.","Strawbridge RJ, Ward J, Ferguson A, Graham N, Shaw RJ, Cullen B, Pearsall R, Lyall LM, Johnston KJA, Niedzwiedz CL, Pell JP, Mackay D, Martin JL, Lyall DM, Bailey MES, Smith DJ.",,EBioMedicine,2019,2019-02-08,Y,,Understanding the Causes of Disease,,"

Background

Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic.

Methods

Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts that life was not worth living' (N = 21,063); 'ever contemplated self-harm' (N = 13,038); 'act of deliberate self-harm in the past' (N = 2498); and 'previous suicide attempt' (N = 2666).

Outcomes

We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81).

Interpretation

These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. FUND: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).",,doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render 34688720,https://doi.org/10.1016/j.ijcard.2021.10.029,Methodological issues in meta-analyses of real-world clinical data to infer causality.,"Uijl A, Lund LH, Asselbergs FW, Savarese G.",,International journal of cardiology,2021,2021-10-22,N,Meta-analysis; Causality; Observational; Sacubitril/valsartan,,,,,doi:https://doi.org/10.1016/j.ijcard.2021.10.029 34019073,https://doi.org/10.1093/ibd/izab059,Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis-An Exploratory Study to Define Deep Remission.,"Iacucci M, Jeffery L, Acharjee A, Nardone OM, Zardo D, Smith SCL, Bazarova A, Cannatelli R, Shivaji UN, Williams J, Gkoutos G, Ghosh S.",,Inflammatory bowel diseases,2021,2021-10-01,Y,Rna-sequencing; Mucosal Healing; Histological Healing; Noninvasive Markers; Endocytoscope,,,"

Background

Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores.

Methods

Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI).Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways.

Results

Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51-0.98) and NHI (r = 0.86; 95% CI, 0.42-0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27-0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa.

Conclusions

Endocytoscopy represents an interesting tool that may sit between endoscopy and histology-but closer to the latter-identifying gene expression markers and pathways that are also identified by histology.",,doi:https://doi.org/10.1093/ibd/izab059; html:https://europepmc.org/articles/PMC8528147; pdf:https://europepmc.org/articles/PMC8528147?pdf=render 35152298,https://doi.org/10.1093/ehjci/jeac030,Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.,"Bourfiss M, Prakken NHJ, James CA, Planken RN, Boekholdt SM, Ahmetagic D, van den Berg MP, Tichnell C, Van der Heijden JF, Loh P, Murray B, Tandri H, Kamel I, Calkins H, Asselbergs FW, Zimmerman SL, Velthuis BK, Te Riele ASJM.",,European heart journal. Cardiovascular Imaging,2022,2022-12-01,Y,Strain; Arrhythmias; Cardiac Magnetic Resonance Imaging; Arrhythmogenic Right Ventricular Cardiomyopathy; Feature Tracking,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients.

Methods and results

CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18).

Conclusion

Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.",,doi:https://doi.org/10.1093/ehjci/jeac030; html:https://europepmc.org/articles/PMC9762936; pdf:https://europepmc.org/articles/PMC9762936?pdf=render 31714636,https://doi.org/10.1002/ana.25642,Lipid lowering and Alzheimer disease risk: A mendelian randomization study.,"Williams DM, Finan C, Schmidt AF, Burgess S, Hingorani AD.",,Annals of neurology,2020,2020-01-01,Y,,,,"

Objective

To examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics.

Methods

We conducted Mendelian randomization analyses using variants in genes that encode the protein targets of several approved lipid-lowering drug classes: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1 (encoding the target for ezetimibe), and APOB (encoding the target of mipomersen). Variants were weighted by associations with low-density lipoprotein cholesterol (LDL-C) using data from lipid genetics consortia (n up to 295,826). We meta-analyzed Mendelian randomization estimates for regional variants weighted by LDL-C on AD risk from 2 large samples (total n = 24,718 cases, 56,685 controls).

Results

Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23-1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.

Interpretation

We did not identify genetic support for the repurposing of statins, ezetimibe, or mipomersen for AD prevention. Notwithstanding caveats to this genetic evidence, pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted. ANN NEUROL 2020;87:30-39.",,doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render -36457326,https://doi.org/10.3389/fpubh.2022.1017337,Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.,"Cerbino-Neto J, Peres IT, Varela MC, Brandão LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",,Frontiers in public health,2022,2022-11-14,Y,Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19,,,"

Background

A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.

Objective

We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.

Methods

We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.

Results

We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).

Conclusions

Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",,doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render 32611631,https://doi.org/10.1212/wnl.0000000000009814,"Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke subtypes.","Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans M.",,Neurology,2020,2020-07-01,Y,,,,"

Objective

We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology.

Methods

We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH).

Results

Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not β-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH.

Conclusions

This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.",,doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render +36457326,https://doi.org/10.3389/fpubh.2022.1017337,Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.,"Cerbino-Neto J, Peres IT, Varela MC, Brandão LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",,Frontiers in public health,2022,2022-11-14,Y,Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19,,,"

Background

A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.

Objective

We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.

Methods

We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.

Results

We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).

Conclusions

Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",,doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render 34606520,https://doi.org/10.1371/journal.pmed.1003815,"COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.","Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",,PLoS medicine,2021,2021-10-04,Y,,,,"

Background

Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).

Methods and findings

We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.

Conclusions

COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",,doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render 35381001,https://doi.org/10.1371/journal.pgen.1010093,Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.,"Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.",,PLoS genetics,2022,2022-04-05,Y,,,,"Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.",,doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render 36814324,https://doi.org/10.1186/s13195-023-01184-y,"Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.","Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.",,Alzheimer's research & therapy,2023,2023-02-22,Y,Metabolites; Ageing; Brain imaging; Alzheimer’s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis,,,"

Background

Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).

Methods

Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).

Results

In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.

Conclusions

Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.",,doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render @@ -1262,33 +1265,33 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34950917,https://doi.org/10.1016/j.lanepe.2021.100248,"Late effects of cancer in children, teenagers and young adults: Population-based study on the burden of 183 conditions, in-patient and critical care admissions and years of life lost.","Chang WH, Katsoulis M, Tan YY, Mueller SH, Green K, Lai AG.",,The Lancet regional health. Europe,2022,2021-11-14,Y,"Primary Care; Hospitalisation; Cancer Treatment; Years Of Life Lost; Cancer Late Effects; Children, Teenagers And Young Adults",,,"

Background

Children, teenagers and young adults who survived cancer are prone to developing late effects. The burden of late effects across a large number of conditions, in-patient hospitalisation and critical care admissions have not been described using a population-based dataset. We aim to systematically quantify the cumulative burden of late effects across all cancer subtypes, treatment modalities and chemotherapy drug classes.

Methods

We employed primary care records linked to hospitals, the death registry and cancer registry from 1998-2020. CTYA survivors were 25 years or younger at the time of cancer diagnosis had survived ≥5 years post-diagnosis. Year-of-birth and sex-matched community controls were used for comparison. We considered nine treatment types, nine chemotherapy classes and 183 physical and mental health late effects. Cumulative burden was estimated using mean cumulative count, which considers recurring events. Multivariable logistic regression was used to investigate the association between treatment exposures and late effects. Excess years of life lost (YLL) attributable to late effects were estimated.

Findings

Among 4,063 patients diagnosed with cancer, 3,466 survived ≥ 5 years (85%); 13,517 matched controls were identified. The cumulative burden of late effects at age 35 was the highest in survivors of leukaemia (23.52 per individual [95% CI:19.85-29.33]) and lowest in survivors of germ cell tumours (CI:6.04 [5.32-6.91]). In controls, the cumulative burden was 3.99 (CI:3.93-4.08) at age 35 years. When survivors reach age 45, the cumulative burden for immunological conditions and infections was the highest (3.27 [CI:3.01-3.58]), followed by cardiovascular conditions (3.08 [CI:1.98-3.29]). Survivors who received chemotherapy and radiotherapy had the highest disease burden compared to those who received surgery only. These patients also had the highest burden of hospitalisation (by age 45: 10.43 [CI:8.27-11.95]). Survivors who received antimetabolite chemotherapy had the highest disease and hospitalisation burden, while the lowest burden is observed in those receiving antitumour antibiotics. Regression analyses revealed that survivors who received only surgery had lower odds of developing cardiovascular (adjusted odds ratio 0.73 [CI:0.56-0.94]), haematological (aOR 0.51 [CI:0.37-0.70]), immunology and infection (aOR 0.84 [CI:0.71-0.99]) and renal (aOR 0.51 [CI:0.39-0.66]) late effects. By contrast, the opposite trend was observed in survivors who received chemo-radiotherapy. High antimetabolite chemotherapy cumulative dose was associated with increased risks of subsequent cancer (aOR 2.32 [CI:1.06-4.84]), metastatic cancer (aOR 4.44 [CI:1.29-11.66]) and renal (aOR 3.48 [CI:1.36-7.86]) conditions. Patients who received radiation dose of ≥50 Gy experienced higher risks of developing metastatic cancer (aOR 5.51 [CI:2.21-11.86]), cancer (aOR 3.77 [CI:2.22-6.34]), haematological (aOR 3.43 [CI:1.54-6.83]) and neurological (aOR 3.24 [CI:1.78-5.66]) conditions. Similar trends were observed in survivors who received more than three teletherapy fields. Cumulative burden analyses on 183 conditions separately revealed varying dominance of different late effects across cancer types, socioeconomic deprivation and treatment modalities. Late effects are associated with excess YLL (i.e., the difference in YLL between survivors with or without late effects), which was the most pronounced among survivors with haematological comorbidities.

Interpretation

To our knowledge, this is the first study to dissect and quantify the importance of late morbidities on subsequent survival using linked electronic health records from multiple settings. The burden of late effects is heterogeneous, as is the risk of premature mortality associated with late effects. We provide an extensive knowledgebase to help inform treatment decisions at the point of diagnosis, future interventional trials and late-effects screening centred on the holistic needs of this vulnerable population.",,doi:https://doi.org/10.1016/j.lanepe.2021.100248; html:https://europepmc.org/articles/PMC8672041; pdf:https://europepmc.org/articles/PMC8672041?pdf=render 33033797,https://doi.org/10.1016/j.eclinm.2020.100560,Investigating the effects of comprehensive smoke-free legislation on neonatal and infant mortality in Thailand using the synthetic control method.,"Radó MK, van Lenthe FJ, Sheikh A, Been JV.",,EClinicalMedicine,2020,2020-10-02,Y,Thailand; Infant Mortality; Child Health; Smoke-free Legislation; Synthetic Control Method,,,"

Background

Almost all of the evidence on the benefits of smoke-free legislation on child health comes from evaluations in high-income countries. We investigated the effects of Thailand's 2010 comprehensive smoke-free legislation on neonatal and infant mortality.

Methods

To overcome some of the methodological issues inherent to traditional quasi-experimental methods, we applied the novel synthetic control approach. Using 2001-2017 country-level panel data from the World Bank and Penn World datasets, we estimated the effects of smoke-free legislation as the difference between the outcome trends in Thailand versus those in a synthetic control country. The synthetic control country was composed of 'control' middle-income countries without comprehensive smoke-free legislation to recreate trends in Thailand in the 2001-2009 pre-legislation outcomes and covariates. We compared the legislation effects to 'placebo effects' obtained for each control country by fictitiously assuming that comprehensive smoke-free legislation was introduced there in 2010, similar to Thailand.

Findings

Neonatal and infant mortality decreased by 2.9% and 2.8%/year respectively following smoke-free legislation, with an estimated 7463 infant deaths (including 4623 neonatal deaths) having been averted over eight years. The results were robust to different specifications of the control countries. Comparison with placebo effects indicated that the findings were unlikely to be attributable to factors other than the smoke-free legislation.

Interpretation

Expanding comprehensive smoke-free policies to middle-income countries can support national efforts to achieve Sustainable Development Goal 3.2 for reducing preventable early-life deaths.

Funding

Netherlands Lung Foundation, HDRUK, Asthma UK center for Applied Research and NIHR Global Respiratory Health Unit (RESPIRE).",,doi:https://doi.org/10.1016/j.eclinm.2020.100560; html:https://europepmc.org/articles/PMC7533363; pdf:https://europepmc.org/articles/PMC7533363?pdf=render 30928915,https://doi.org/10.1136/injuryprev-2018-043085,Comparison of revised Functional Capacity Index scores with Abbreviated Injury Scale 2008 scores in predicting 12-month severe trauma outcomes.,"Palmer CS, Cameron PA, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2020,2019-03-30,N,Trauma Registry; Trauma Scoring; Functional Outcomes; Prediction Models; Abbreviated Injury Scale; Major Trauma; Functional Capacity Index; 12-Month Outcomes,,,"

Introduction

Anatomical injury as measured by the AIS often accounts for only a small proportion of variability in outcomes after injury. The predictive Functional Capacity Index (FCI) appended to the 2008 AIS claims to provide a widely available method of predicting 12-month function following injury.

Objectives

To determine the extent to which AIS-based and FCI-based scoring is able to add to a simple predictive model of 12-month function following severe injury.

Methods

Adult trauma patients were drawn from the population-based Victorian State Trauma Registry. Major trauma and severely injured orthopaedic trauma patients were followed up via telephone interview including Glasgow Outcome Scale-Extended, the EQ-5D-3L and return to work status. A battery of AIS-based and FCI-based scores, and a simple count of AIS-coded injuries were added in turn to a base model using age and gender.

Results

A total of 20 813 patients survived to 12 months and had at least one functional outcome recorded, representing 85% follow-up. Predictions using the base model varied substantially across outcome measures. Irrespective of the method used to classify the severity of injury, adding injury severity to the model significantly, but only slightly improved model fit. Across the outcomes evaluated, no method of injury severity assessment consistently outperformed any other.

Conclusions

Anatomical injury is a predictor of trauma outcome. However, injury severity as described by the FCI does not consistently improve discrimination, or even provide the best discrimination compared with AIS-based severity scores or a simple injury count.",,doi:https://doi.org/10.1136/injuryprev-2018-043085 +36711167,https://doi.org/10.1093/ehjdh/ztaa016,Real-time imputation of missing predictor values in clinical practice.,"Nijman SWJ, Hoogland J, Groenhof TKJ, Brandjes M, Jacobs JJL, Bots ML, Asselbergs FW, Moons KGM, Debray TPA.",,European heart journal. Digital health,2021,2020-12-19,Y,Prediction; Missing Data; Electronic Health Records; Computerized Decision Support System; Real-time Imputation; Joint Modelling Imputation,,,"

Aims

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors, which is not always available in daily practice. We aim to describe two methods for real-time handling of missing predictor values when using prediction models in practice.

Methods and results

We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modelling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance [mean squared error (MSE) of linear predictor], discrimination (c-index), calibration (intercept and slope), and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs. 0.68), and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar.

Conclusions

We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.",,doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render 37339333,https://doi.org/10.1002/jia2.26104,"COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.","Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,Journal of the International AIDS Society,2023,2023-06-01,Y,Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2,,,"

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.",,doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render 37201609,https://doi.org/10.1016/j.ijcard.2023.05.024,Identifying distinct clinical clusters in heart failure with mildly reduced ejection fraction.,"Meijs C, Brugts JJ, Lund LH, Linssen GCM, Rocca HB, Dahlström U, Vaartjes I, Koudstaal S, Asselbergs FW, Savarese G, Uijl A.",,International journal of cardiology,2023,2023-05-16,N,Heterogeneity; Clustering; Latent Class Analysis; Heart Failure With Mildly Reduced Ejection Fraction,,,"

Introduction

Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis.

Methods and results

Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets.

Conclusion

We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design.",,doi:https://doi.org/10.1016/j.ijcard.2023.05.024 -36711167,https://doi.org/10.1093/ehjdh/ztaa016,Real-time imputation of missing predictor values in clinical practice.,"Nijman SWJ, Hoogland J, Groenhof TKJ, Brandjes M, Jacobs JJL, Bots ML, Asselbergs FW, Moons KGM, Debray TPA.",,European heart journal. Digital health,2021,2020-12-19,Y,Prediction; Missing Data; Electronic Health Records; Computerized Decision Support System; Real-time Imputation; Joint Modelling Imputation,,,"

Aims

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors, which is not always available in daily practice. We aim to describe two methods for real-time handling of missing predictor values when using prediction models in practice.

Methods and results

We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modelling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance [mean squared error (MSE) of linear predictor], discrimination (c-index), calibration (intercept and slope), and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs. 0.68), and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar.

Conclusions

We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.",,doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render 31711543,https://doi.org/10.1186/s13326-019-0214-4,Natural language processing for disease phenotyping in UK primary care records for research: a pilot study in myocardial infarction and death.,"Shah AD, Bailey E, Williams T, Denaxas S, Dobson R, Hemingway H.",,Journal of biomedical semantics,2019,2019-11-12,Y,Myocardial infarction; Chest pain; Primary Care; Natural Language Processing; Free Text,Applied Analytics,,"

Background

Free text in electronic health records (EHR) may contain additional phenotypic information beyond structured (coded) information. For major health events - heart attack and death - there is a lack of studies evaluating the extent to which free text in the primary care record might add information. Our objectives were to describe the contribution of free text in primary care to the recording of information about myocardial infarction (MI), including subtype, left ventricular function, laboratory results and symptoms; and recording of cause of death. We used the CALIBER EHR research platform which contains primary care data from the Clinical Practice Research Datalink (CPRD) linked to hospital admission data, the MINAP registry of acute coronary syndromes and the death registry. In CALIBER we randomly selected 2000 patients with MI and 1800 deaths. We implemented a rule-based natural language engine, the Freetext Matching Algorithm, on site at CPRD to analyse free text in the primary care record without raw data being released to researchers. We analysed text recorded within 90 days before or 90 days after the MI, and on or after the date of death.

Results

We extracted 10,927 diagnoses, 3658 test results, 3313 statements of negation, and 850 suspected diagnoses from the myocardial infarction patients. Inclusion of free text increased the recorded proportion of patients with chest pain in the week prior to MI from 19 to 27%, and differentiated between MI subtypes in a quarter more patients than structured data alone. Cause of death was incompletely recorded in primary care; in 36% the cause was in coded data and in 21% it was in free text. Only 47% of patients had exactly the same cause of death in primary care and the death registry, but this did not differ between coded and free text causes of death.

Conclusions

Among patients who suffer MI or die, unstructured free text in primary care records contains much information that is potentially useful for research such as symptoms, investigation results and specific diagnoses. Access to large scale unstructured data in electronic health records (millions of patients) might yield important insights.", NLP methods were used to analyse free text from hospital records for people with MI. They analysed text recorded within 90 days bfore or 90 days after the MI and found that free text in hospital records contains unformation useful for diagnoses,doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render 33372069,https://doi.org/10.1136/bmjopen-2020-038360,Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study.,"Fermont JM, Fisk M, Bolton CE, MacNee W, Cockcroft JR, Fuld J, Cheriyan J, Mohan D, Mäki-Petäjä KM, Al-Hadithi AB, Tal-Singer R, Müllerova H, Polkey MI, Wood AM, McEniery CM, Wilkinson IB, ERICA consortium.",,BMJ open,2020,2020-12-28,Y,epidemiology; Primary Care; Cardiac Epidemiology; Chronic Airways Disease; Respiratory Medicine (See Thoracic Medicine),,,"

Objectives

Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.

Design

Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.

Setting

Five UK centres interested in COPD.

Participants

Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.

Interventions

Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.

Primary and secondary outcome measures

New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.

Results

Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).

Conclusion

Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.

Trial registration number

ID 11101.",,doi:https://doi.org/10.1136/bmjopen-2020-038360; html:https://europepmc.org/articles/PMC7772292; pdf:https://europepmc.org/articles/PMC7772292?pdf=render 32738956,https://doi.org/10.1016/s0140-6736(20)31286-1,Atopic dermatitis.,"Langan SM, Irvine AD, Weidinger S.",,"Lancet (London, England)",2020,2020-08-01,N,,,,"Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.",,doi:https://doi.org/10.1016/S0140-6736(20)31286-1 36029662,https://doi.org/10.1016/j.bios.2022.114623,Triazole-derivatized near-infrared cyanine dyes enable local functional fluorescent imaging of ocular inflammation.,"Thomas CN, Alfahad N, Capewell N, Cowley J, Hickman E, Fernandez A, Harrison N, Qureshi OS, Bennett N, Barnes NM, Dick AD, Chu CJ, Liu X, Denniston AK, Vendrell M, Hill LJ.",,Biosensors & bioelectronics,2022,2022-08-13,N,Leukocytes; Uveitis; Cyanine; Near-infrared; optical coherence tomography; Fluorophores,,,"Near-infrared (NIR) chemical fluorophores are promising tools for in-vivo imaging in real time but often succumb to rapid photodegradation. Indocyanine green (ICG) is the only NIR dye with regulatory approval for ocular imaging in humans; however, ICG, when employed for applications such as labelling immune cells, has limited sensitivity and does not allow precise detection of specific inflammatory events, for example leukocyte recruitment during uveitic flare-ups. We investigated the potential use of photostable novel triazole NIR cyanine (TNC) dyes for detecting and characterising activated T-cell activity within the eye. Three TNC dyes were evaluated for ocular cytotoxicity in-vitro using a MTT assay and optimised concentrations for intraocular detection within ex-vivo porcine eyes after topical application or intracameral injections of the dyes. TNC labelled T-cell tracking experiments and mechanistic studies were also performed in-vitro. TNC-1 and TNC-2 dyes exhibited greater fluorescence intensity than ICG at 10 μM, whereas TNC-3 was only detectable at 100 μM within the porcine eye. TNC dyes did not demonstrate any ocular cell toxicity at working concentrations of 10 μM. CD4+T-cells labelled with TNC-1 or TNC-2 were detected within the porcine eye, with TNC-1 being brighter than TNC-2. Detection of TNC-1 and TNC-2 into CD4+T-cells was prevented by prior incubation with dynole 34-2 (50 μM), suggesting active uptake of these dyes via dynamin-dependent processes. The present study provides evidence that TNC dyes are suitable to detect activated CD4+T-cells within the eye with potential as a diagnostic marker for ocular inflammatory diseases.",,doi:https://doi.org/10.1016/j.bios.2022.114623 34535484,https://doi.org/10.1136/bmjopen-2021-050647,The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): protocol for a prospective longitudinal cohort study of healthcare and ancillary workers in UK healthcare settings.,"Woolf K, Melbourne C, Bryant L, Guyatt AL, McManus IC, Gupta A, Free RC, Nellums L, Carr S, John C, Martin CA, Wain LV, Gray LJ, Garwood C, Modhwadia V, Abrams KR, Tobin MD, Khunti K, Pareek M, UK-REACH Study Collaborative Group+.",,BMJ open,2021,2021-09-17,Y,Mental health; Public Health; Covid-19,,,"

Introduction

The COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).

Methods and analysis

A baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.

Ethics and dissemination

The study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals.

Trial registration number

ISRCTN11811602; Pre-results.",,doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?pdf=render -36823471,https://doi.org/10.1038/s42255-023-00753-7,Proteogenomic links to human metabolic diseases.,"Koprulu M, Carrasco-Zanini J, Wheeler E, Lockhart S, Kerrison ND, Wareham NJ, Pietzner M, Langenberg C.",,Nature metabolism,2023,2023-02-23,Y,,,,"Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 256 unreported protein quantitative trait loci (pQTL); (2) demonstrate shared genetic regulation of 224 cis-pQTLs with 575 specific health outcomes, revealing examples for notable metabolic diseases (such as gastrin-releasing peptide as a potential therapeutic target for type 2 diabetes); (3) improve causal gene assignment at 40% (n = 192) of overlapping risk loci; and (4) observe convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for 12 proteins, such as TIMD4 for lipoprotein metabolism. Our findings demonstrate the value of integrating complementary proteomic technologies with genomics even at moderate scale to identify new mediators of metabolic diseases with the potential for therapeutic interventions.",,doi:https://doi.org/10.1038/s42255-023-00753-7; html:https://europepmc.org/articles/PMC7614946; pdf:https://europepmc.org/articles/PMC7614946?pdf=render 34753797,https://doi.org/10.2337/db21-0320,An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript.,"Riveros-Mckay F, Roberts D, Di Angelantonio E, Yu B, Soranzo N, Danesh J, Selvin E, Butterworth AS, Barroso I.",,Diabetes,2022,2022-02-01,N,,,,"Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 U.S. White and 2,712 U.S. Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. In this study, we performed a GWAS on 20,731 European-ancestry blood donors and meta-analyzed our results with previous data from U.S. White participants from the Atherosclerosis Risk in Communities (ARIC) study (Nmeta = 29,685). We identified a novel association near GCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49; Pmeta = 3.66 × 10-8) and confirmed the association near RCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17; Pmeta = 5.71 × 10-18). Colocalization analysis with whole-blood expression quantitative trait loci data suggested FCGRT as the effector transcript at the RCN3 locus. We further showed that fructosamine has low heritability (h2 = 7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (P > 0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni-corrected P < 0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize FCGRT for downstream functional studies at the established RCN3 locus.",,doi:https://doi.org/10.2337/db21-0320; html:https://europepmc.org/articles/PMC8914280; pdf:https://europepmc.org/articles/PMC8914280?pdf=render; doi:https://doi.org/10.2337/db21-0320; pdf:https://diabetesjournals.org/diabetes/article-pdf/71/2/359/640867/db210320.pdf 32817390,https://doi.org/10.1212/wnl.0000000000010463,"Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study.","Huang J, Zuber V, Matthews PM, Elliott P, Tzoulaki J, Dehghan A.",,Neurology,2020,2020-08-19,Y,,,,"

Objective

To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD).

Methods

We conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance-weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization-Egger for sensitivity analyses to test for pleiotropic effects.

Results

We found that higher risk of AD was significantly associated with being a ""morning person"" (odds ratio [OR] 1.01, p = 0.001), shorter sleep duration (self-reported: β = -0.006, p = 1.9 × 10-4; accelerometer based: β = -0.015, p = 6.9 × 10-5), less likely to report long sleep (β = -0.003, p = 7.3 × 10-7), earlier timing of the least active 5 hours (β = -0.024, p = 1.7 × 10-13), and a smaller number of sleep episodes (β = -0.025, p = 5.7 × 10-14) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, p = 7 × 10-13). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD.

Conclusion

We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.",,doi:https://doi.org/10.1212/WNL.0000000000010463; html:https://europepmc.org/articles/PMC7682841; pdf:https://europepmc.org/articles/PMC7682841?pdf=render 35115689,https://doi.org/10.1038/s41588-021-00991-z,Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort.,"Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, Tripathi A, Vázquez-Baeza Y, Loomba R, Cheng S, Jain M, Niiranen T, Lahti L, Knight R, Salomaa V, Inouye M, Méric G.",,Nature genetics,2022,2022-02-03,N,,,,"Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.",,doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z +36823471,https://doi.org/10.1038/s42255-023-00753-7,Proteogenomic links to human metabolic diseases.,"Koprulu M, Carrasco-Zanini J, Wheeler E, Lockhart S, Kerrison ND, Wareham NJ, Pietzner M, Langenberg C.",,Nature metabolism,2023,2023-02-23,Y,,,,"Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 256 unreported protein quantitative trait loci (pQTL); (2) demonstrate shared genetic regulation of 224 cis-pQTLs with 575 specific health outcomes, revealing examples for notable metabolic diseases (such as gastrin-releasing peptide as a potential therapeutic target for type 2 diabetes); (3) improve causal gene assignment at 40% (n = 192) of overlapping risk loci; and (4) observe convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for 12 proteins, such as TIMD4 for lipoprotein metabolism. Our findings demonstrate the value of integrating complementary proteomic technologies with genomics even at moderate scale to identify new mediators of metabolic diseases with the potential for therapeutic interventions.",,doi:https://doi.org/10.1038/s42255-023-00753-7; html:https://europepmc.org/articles/PMC7614946; pdf:https://europepmc.org/articles/PMC7614946?pdf=render PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm during the COVID-19 pandemic: a repeat cross-sectional UK population survey","John A, Lee S, Solomon S, Crepaz-Keay D, McDaid S, Morton A, Davidson G, Van Bortel T, Kousoulis A.",,BMJ open,2021,2021-01-01,Y,Mental health; Public Health; Suicide & Self-harm; Covid-19,,,"

Objectives

There has been speculation on the impact of the COVID-19 pandemic and the associated lockdown on suicidal thoughts and self-harm and the factors associated with any change. We aimed to assess the effects and change in effects of risk factors including loneliness and coping, as well as pre-existing mental health conditions on suicidal thoughts and self-harm during the COVID-19 pandemic.

Design

This study was a repeated cross-sectional online population-based survey.

Participants and measures

Non-probability quota sampling was adopted on the UK adult population and four waves of data were analysed during the pandemic (17 March 2020 to 29 May 2020). Outcomes were suicidal thoughts and self-harm associated with the pandemic while loneliness, coping, pre-existing mental health conditions, employment status and demographics were covariates. We ran binomial regressions to evaluate the adjusted risks of the studied covariates as well as the changes in effects over time.

Results

The proportion of individuals who felt lonely increased sharply from 9.8% to 23.9% after the UK lockdown began. Young people (aged 18–24 years), females, students, those who were unemployed and individuals with pre-existing mental health conditions were more likely to report feeling lonely and not coping well. 7.7%–10.0% and 1.9%–2.2% of respondents reported having suicidal thoughts and self-harm associated with the pandemic respectively throughout the period studied. Results from cross-tabulation and adjusted regression analyses showed young adults, coping poorly and with pre-existing mental health conditions were significantly associated with suicidal thoughts and self-harm. Loneliness was significantly associated with suicidal thoughts but not self-harm.

Conclusions

The association between suicidality, loneliness and coping was evident in young people during the early stages of the pandemic. Developing effective interventions designed and coproduced to address loneliness and promote coping strategies during prolonged social isolation may promote mental health and help mitigate suicidal thoughts and self-harm associated with the pandemic.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8718341; pdf:https://europepmc.org/articles/PMC8718341?pdf=render 37348789,https://doi.org/10.1016/j.jhep.2023.05.046,Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.,"Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.",,Journal of hepatology,2023,2023-06-20,N,Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation,,,"

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range:1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.",,doi:https://doi.org/10.1016/j.jhep.2023.05.046 33905476,https://doi.org/10.1093/cid/ciab192,Model-Based Geostatistical Methods Enable Efficient Design and Analysis of Prevalence Surveys for Soil-Transmitted Helminth Infection and Other Neglected Tropical Diseases.,"Johnson O, Fronterre C, Amoah B, Montresor A, Giorgi E, Midzi N, Mutsaka-Makuvaza MJ, Kargbo-Labor I, Hodges MH, Zhang Y, Okoyo C, Mwandawiro C, Minnery M, Diggle PJ.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2021,2021-06-01,Y,Geospatial Analysis; Prevalence Survey; Soil-transmitted Helminth Infection; Model-based Geostatistics; Control Of Neglected Tropical Diseases; Impact Survey,,,"Maps of the geographical variation in prevalence play an important role in large-scale programs for the control of neglected tropical diseases. Precontrol mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed postintervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by 2 kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest, and digital images of environmental factors that are predictive of local prevalence. In this article, we focus on the design and analysis of impact surveys, that is, prevalence surveys that are conducted postintervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analyzed as efficiently as possible so as to make best use of hard-won field data. We use 3 case studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone, and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organization (WHO) guidelines. In all 3 cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other neglected tropical diseases.",,doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render -37494011,https://doi.org/10.1001/jamacardio.2023.2167,"Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.","Aung N, Wang Q, van Duijvenboden S, Burns R, Stoma S, Raisi-Estabragh Z, Ahmet S, Allara E, Wood A, Di Angelantonio E, Danesh J, Munroe PB, Young A, Harvey NC, Codd V, Nelson CP, Petersen SE, Samani NJ.",,JAMA cardiology,2023,2023-07-26,Y,,,,"

Importance

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective

To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants

This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure

LTL.

Main outcomes and measures

Cardiovascular imaging traits and HF.

Results

Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance

In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.",,doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756; pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf 32709646,https://doi.org/10.1136/bmjopen-2019-036099,"Predicting the risk of asthma attacks in children, adolescents and adults: protocol for a machine learning algorithm derived from a primary care-based retrospective cohort.","Hussain Z, Shah SA, Mukherjee M, Sheikh A.",,BMJ open,2020,2020-07-23,Y,Asthma; epidemiology; Public Health; Health Informatics,,,"

Introduction

Most asthma attacks and subsequent deaths are potentially preventable. We aim to develop a prognostic tool for identifying patients at high risk of asthma attacks in primary care by leveraging advances in machine learning.

Methods and analysis

Current prognostic tools use logistic regression to develop a risk scoring model for asthma attacks. We propose to build on this by systematically applying various well-known machine learning techniques to a large longitudinal deidentified primary care database, the Optimum Patient Care Research Database, and comparatively evaluate their performance with the existing logistic regression model and against each other. Machine learning algorithms vary in their predictive abilities based on the dataset and the approach to analysis employed. We will undertake feature selection, classification (both one-class and two-class classifiers) and performance evaluation. Patients who have had actively treated clinician-diagnosed asthma, aged 8-80 years and with 3 years of continuous data, from 2016 to 2018, will be selected. Risk factors will be obtained from the first year, while the next 2 years will form the outcome period, in which the primary endpoint will be the occurrence of an asthma attack.

Ethics and dissemination

We have obtained approval from OPCRD's Anonymous Data Ethics Protocols and Transparency (ADEPT) Committee. We will seek ethics approval from The University of Edinburgh's Research Ethics Group (UREG). We aim to present our findings at scientific conferences and in peer-reviewed journals.",,doi:https://doi.org/10.1136/bmjopen-2019-036099; html:https://europepmc.org/articles/PMC7380838; pdf:https://europepmc.org/articles/PMC7380838?pdf=render -36764723,https://doi.org/10.1136/bmjopen-2022-067254,Associations of remote mental healthcare with clinical outcomes: a natural language processing enriched electronic health record data study protocol.,"Ahmed MS, Kornblum D, Oliver D, Fusar-Poli P, Patel R.",,BMJ open,2023,2023-02-10,Y,Psychiatry; epidemiology; Telemedicine; Health Informatics,,,"

Introduction

People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.

Methods and analysis

Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80 000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5 million documents to analyse the variation in content of remote versus in-person assessments.

Ethics and dissemination

The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.",,doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render +37494011,https://doi.org/10.1001/jamacardio.2023.2167,"Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.","Aung N, Wang Q, van Duijvenboden S, Burns R, Stoma S, Raisi-Estabragh Z, Ahmet S, Allara E, Wood A, Di Angelantonio E, Danesh J, Munroe PB, Young A, Harvey NC, Codd V, Nelson CP, Petersen SE, Samani NJ.",,JAMA cardiology,2023,2023-07-26,Y,,,,"

Importance

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective

To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants

This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure

LTL.

Main outcomes and measures

Cardiovascular imaging traits and HF.

Results

Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance

In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.",,doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756; pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf 33206055,https://doi.org/10.2196/19650,Mobile Clinical Decision Support System for the Management of Diabetic Patients With Kidney Complications in UK Primary Care Settings: Mixed Methods Feasibility Study.,"Alhodaib HI, Antza C, Chandan JS, Hanif W, Sankaranarayanan S, Paul S, Sutcliffe P, Nirantharakumar K.",,JMIR diabetes,2020,2020-11-18,Y,Diabetes mellitus; Chronic Kidney Disease; Feasibility Study; Ehealth; Clinical Decision Support Application,,,"

Background

Attempts to utilize eHealth in diabetes mellitus (DM) management have shown promising outcomes, mostly targeted at patients; however, few solutions have been designed for health care providers.

Objective

The purpose of this study was to conduct a feasibility project developing and evaluating a mobile clinical decision support system (CDSS) tool exclusively for health care providers to manage chronic kidney disease (CKD) in patients with DM.

Methods

The design process was based on the 3 key stages of the user-centered design framework. First, an exploratory qualitative study collected the experiences and views of DM specialist nurses regarding the use of mobile apps in clinical practice. Second, a CDSS tool was developed for the management of patients with DM and CKD. Finally, a randomized controlled trial examined the acceptability and impact of the tool.

Results

We interviewed 15 DM specialist nurses. DM specialist nurses were not currently using eHealth solutions in their clinical practice, while most nurses were not even aware of existing medical apps. However, they appreciated the potential benefits that apps may bring to their clinical practice. Taking into consideration the needs and preferences of end users, a new mobile CDSS app, ""Diabetes & CKD,"" was developed based on guidelines. We recruited 39 junior foundation year 1 doctors (44% male) to evaluate the app. Of them, 44% (17/39) were allocated to the intervention group, and 56% (22/39) were allocated to the control group. There was no significant difference in scores (maximum score=13) assessing the management decisions between the app and paper-based version of the app's algorithm (intervention group: mean 7.24 points, SD 2.46 points; control group: mean 7.39, SD 2.56; t37=-0.19, P=.85). However, 82% (14/17) of the participants were satisfied with using the app.

Conclusions

The findings will guide the design of future CDSS apps for the management of DM, aiming to help health care providers with a personalized approach depending on patients' comorbidities, specifically CKD, in accordance with guidelines.",,doi:https://doi.org/10.2196/19650; html:https://europepmc.org/articles/PMC7710444; pdf:https://europepmc.org/articles/PMC7710444?pdf=render +36764723,https://doi.org/10.1136/bmjopen-2022-067254,Associations of remote mental healthcare with clinical outcomes: a natural language processing enriched electronic health record data study protocol.,"Ahmed MS, Kornblum D, Oliver D, Fusar-Poli P, Patel R.",,BMJ open,2023,2023-02-10,Y,Psychiatry; epidemiology; Telemedicine; Health Informatics,,,"

Introduction

People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.

Methods and analysis

Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80 000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5 million documents to analyse the variation in content of remote versus in-person assessments.

Ethics and dissemination

The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.",,doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render 32345651,https://doi.org/10.2337/dc19-2116,"Obstructive Sleep Apnea, a Risk Factor for Cardiovascular and Microvascular Disease in Patients With Type 2 Diabetes: Findings From a Population-Based Cohort Study.","Adderley NJ, Subramanian A, Toulis K, Gokhale K, Taverner T, Hanif W, Haroon S, Thomas GN, Sainsbury C, Tahrani AA, Nirantharakumar K.",,Diabetes care,2020,2020-04-28,N,,,,"

Objective

To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA.

Research design and methods

This age-, sex-, BMI-, and diabetes duration-matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.

Results

A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3-5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed.

Conclusions

Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.",,doi:https://doi.org/10.2337/dc19-2116 32814581,https://doi.org/10.1186/s12916-020-01687-7,Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.,"Dawa J, Emukule GO, Barasa E, Widdowson MA, Anzala O, van Leeuwen E, Baguelin M, Chaves SS, Eggo RM.",,BMC medicine,2020,2020-08-20,Y,Economic evaluation; Influenza vaccine; Cost-effectiveness; Low- And Middle-income Countries; Dynamic Transmission Model; Vaccine Timing; Vaccine Target Group,,,"

Background

There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya.

Methods

We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872).

Results

The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit.

Conclusion

Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.",,doi:https://doi.org/10.1186/s12916-020-01687-7; html:https://europepmc.org/articles/PMC7438179; pdf:https://europepmc.org/articles/PMC7438179?pdf=render 33148619,https://doi.org/10.1136/bmj.m3919,Consistency of variety of machine learning and statistical models in predicting clinical risks of individual patients: longitudinal cohort study using cardiovascular disease as exemplar.,"Li Y, Sperrin M, Ashcroft DM, van Staa TP.",,BMJ (Clinical research ed.),2020,2020-11-04,Y,,,,"

Objective

To assess the consistency of machine learning and statistical techniques in predicting individual level and population level risks of cardiovascular disease and the effects of censoring on risk predictions.

Design

Longitudinal cohort study from 1 January 1998 to 31 December 2018.

Setting and participants

3.6 million patients from the Clinical Practice Research Datalink registered at 391 general practices in England with linked hospital admission and mortality records.

Main outcome measures

Model performance including discrimination, calibration, and consistency of individual risk prediction for the same patients among models with comparable model performance. 19 different prediction techniques were applied, including 12 families of machine learning models (grid searched for best models), three Cox proportional hazards models (local fitted, QRISK3, and Framingham), three parametric survival models, and one logistic model.

Results

The various models had similar population level performance (C statistics of about 0.87 and similar calibration). However, the predictions for individual risks of cardiovascular disease varied widely between and within different types of machine learning and statistical models, especially in patients with higher risks. A patient with a risk of 9.5-10.5% predicted by QRISK3 had a risk of 2.9-9.2% in a random forest and 2.4-7.2% in a neural network. The differences in predicted risks between QRISK3 and a neural network ranged between -23.2% and 0.1% (95% range). Models that ignored censoring (that is, assumed censored patients to be event free) substantially underestimated risk of cardiovascular disease. Of the 223 815 patients with a cardiovascular disease risk above 7.5% with QRISK3, 57.8% would be reclassified below 7.5% when using another model.

Conclusions

A variety of models predicted risks for the same patients very differently despite similar model performances. The logistic models and commonly used machine learning models should not be directly applied to the prediction of long term risks without considering censoring. Survival models that consider censoring and that are explainable, such as QRISK3, are preferable. The level of consistency within and between models should be routinely assessed before they are used for clinical decision making.",,doi:https://doi.org/10.1136/bmj.m3919; html:https://europepmc.org/articles/PMC7610202 35072137,https://doi.org/10.1016/j.xgen.2021.100086,Machine learning optimized polygenic scores for blood cell traits identify sex-specific trajectories and genetic correlations with disease.,"Xu Y, Vuckovic D, Ritchie SC, Akbari P, Jiang T, Grealey J, Butterworth AS, Ouwehand WH, Roberts DJ, Di Angelantonio E, Danesh J, Soranzo N, Inouye M.",,Cell genomics,2022,2022-01-12,Y,Method; Machine Learning; Population Stratification; Polygenic Score; Blood Cell Trait; Disease Assocations,,,"Genetic association studies for blood cell traits, which are key indicators of health and immune function, have identified several hundred associations and defined a complex polygenic architecture. Polygenic scores (PGSs) for blood cell traits have potential clinical utility in disease risk prediction and prevention, but designing PGS remains challenging and the optimal methods are unclear. To address this, we evaluated the relative performance of 6 methods to develop PGS for 26 blood cell traits, including a standard method of pruning and thresholding (P + T) and 5 learning methods: LDpred2, elastic net (EN), Bayesian ridge (BR), multilayer perceptron (MLP) and convolutional neural network (CNN). We evaluated these optimized PGSs on blood cell trait data from UK Biobank and INTERVAL. We find that PGSs designed using common machine learning methods EN and BR show improved prediction of blood cell traits and consistently outperform other methods. Our analyses suggest EN/BR as the top choices for PGS construction, showing improved performance for 25 blood cell traits in the external validation, with correlations with the directly measured traits increasing by 10%-23%. Ten PGSs showed significant statistical interaction with sex, and sex-specific PGS stratification showed that all of them had substantial variation in the trajectories of blood cell traits with age. Genetic correlations between the PGSs for blood cell traits and common human diseases identified well-known as well as new associations. We develop machine learning-optimized PGS for blood cell traits, demonstrate their relationships with sex, age, and disease, and make these publicly available as a resource.",,doi:https://doi.org/10.1016/j.xgen.2021.100086; html:https://europepmc.org/articles/PMC8758502; pdf:https://europepmc.org/articles/PMC8758502?pdf=render -36449515,https://doi.org/10.1371/journal.pcbi.1010726,Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.,"Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.",,PLoS computational biology,2022,2022-11-30,Y,,,,"The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.",,doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render 32017129,https://doi.org/10.5694/mja2.50485,Discharge destination and patient-reported outcomes after inpatient treatment for isolated lower limb fractures.,"Kimmel LA, Simpson PM, Holland AE, Edwards ER, Cameron PA, de Steiger RS, Page RS, Hau R, Bucknill A, Kasza J, Gabbe BJ.",,The Medical journal of Australia,2020,2020-02-04,N,"Rehabilitation; Treatment outcome; Orthopedic Procedures; Fractures, Bone; Trauma Surgery",,,"

Objectives

To examine the association between discharge destination (home or inpatient rehabilitation) for adult patients treated in hospital for isolated lower limb fractures and patient-reported outcomes.

Design

Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.

Setting, participants

Adults (18-64 years old) treated for isolated lower limb fractures at four Melbourne trauma hospitals that contribute data to the VOTOR, 1 March 2007 - 31 March 2016.

Main outcome measures

Return to work and functional recovery (assessed with the extended Glasgow Outcomes Scale, GOS-E); propensity score analysis of association between discharge destination and outcome.

Results

Of 7961 eligible patients, 1432 (18%) were discharged to inpatient rehabilitation, and 6775 (85%) were followed up 12 months after their injuries. After propensity score adjustment, the odds of better functional recovery were 56% lower for patients discharged to inpatient rehabilitation than for those discharged directly home (odds ratio, 0.44; 95% CI, 0.37-0.51); for the 5057 people working before their accident, the odds of return to work were reduced by 66% (odds ratio, 0.34; 95% CI, 0.26-0.46). Propensity score analysis improved matching of the discharge destination groups, but imbalances in funding source remained for both outcome analyses, and for also for site and cause of injury in the GOS-E analysis (standardised differences, 10-16%).

Conclusions

Discharge to inpatient rehabilitation after treatment for isolated lower limb fractures was associated with poorer outcomes than discharge home. Factors that remained unbalanced after propensity score analysis could be assessed in controlled trials.",,doi:https://doi.org/10.5694/mja2.50485 -32234121,https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256,"Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.","Russell TW, Hellewell J, Jarvis CI, van Zandvoort K, Abbott S, Ratnayake R, CMMID COVID-19 working group, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-03-01,Y,Coronavirus; outbreak; Severity; Asymptomatic; Case Fatality Ratio; Cruise Ship; Covid-19; Infection Fatality Ratio,"COVID-19, Improving Public Health","COVID-19, infection","Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.",,doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render; pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance +36449515,https://doi.org/10.1371/journal.pcbi.1010726,Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.,"Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.",,PLoS computational biology,2022,2022-11-30,Y,,,,"The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.",,doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render 31747863,https://doi.org/10.1161/jaha.119.012551,"UVA and Seasonal Patterning of 56 370 Myocardial Infarctions Across Scotland, 2000-2011.","Mackay DF, Clemens TL, Hastie CE, Cherrie MPC, Dibben C, Pell JP.",,Journal of the American Heart Association,2019,2019-11-21,Y,Environmental factors; UV radiation; Myocardial infarction; epidemiology,"Improving Public Health, Understanding the Causes of Disease",,"Background Myocardial infarction exhibits seasonal patterning, with higher amplitude at increased latitude. Epidemiological evidence suggests that sunlight is protective against cardiovascular disease, independent of ambient temperature, but ultraviolet B-mediated vitamin D production has been discounted as causal. We aimed to determine whether ultraviolet A is associated with the seasonal patterning of myocardial infarction. Methods and Results Routine hospitalization data were used to determine monthly incidence of myocardial infarction in Scotland between 2000 and 2011. Small-area-level aggregated data were obtained on ambient temperature from the Meteorological Office and ultraviolet A and ultraviolet B irradiance from NASA satellites. Autoregressive distributed lag models were run for ultraviolet A and myocardial infarction, including adjustment for ambient temperature and ultraviolet B. Monthly incidence of myocardial infarction displayed winter peaks and summer troughs superimposed on the underlying trend, with a mean amplitude of 0.31 (95% CI: 0.21, 0.41) myocardial infarctions per 100 000 population per month. Ultraviolet A exposure was inversely associated with myocardial infarction independent of ambient temperature (coefficient, -0.05; 95% CI, -0.09, -0.01; P=0.015) and ultraviolet B UVB (coefficient, -0.05; 95% CI, -0.09, -0.02; P=0.004). Conclusions Further research is required to explore whether an ultraviolet-mediated mechanism different to vitamin D, such as nitric oxide-mediated vasodilatation, may play a causal role in the seasonal and geographical patterning of myocardial infarction.",,doi:https://doi.org/10.1161/JAHA.119.012551; html:https://europepmc.org/articles/PMC6912961; pdf:https://europepmc.org/articles/PMC6912961?pdf=render +32234121,https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256,"Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.","Russell TW, Hellewell J, Jarvis CI, van Zandvoort K, Abbott S, Ratnayake R, CMMID COVID-19 working group, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-03-01,Y,Coronavirus; outbreak; Severity; Asymptomatic; Case Fatality Ratio; Cruise Ship; Covid-19; Infection Fatality Ratio,"COVID-19, Improving Public Health","COVID-19, infection","Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.",,doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render; pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance 31984563,https://doi.org/10.1111/jce.14368,Early recurrences of atrial tachyarrhythmias post pulmonary vein isolation.,"von Olshausen G, Uijl A, Jensen-Urstad M, Schwieler J, Drca N, Bastani H, Tapanainen J, Saluveer O, Bourke T, Kennebäck G, Insulander P, Deisenhofer I, Braunschweig F.",,Journal of cardiovascular electrophysiology,2020,2020-01-31,N,Atrial fibrillation; Catheter ablation; Late Recurrence; Early Recurrence; Blanking Period,,,"

Aims

To investigate the significance of early recurrence (ER) of atrial tachyarrhythmias after pulmonary vein isolation (PVI) on the development of late recurrence (LR) and to redefine the blanking period during which an ER is considered nonspecific.

Methods

Data of 713 patients undergoing their first PVI for paroxysmal or persistent atrial fibrillation between January 2012 and December 2017 were included. All patients were followed-up for 12 months according to clinical and outpatient routine and were screened for any atrial tachyarrhythmia lasting >30 seconds occurring during the first 3 months postablation (ER) and after the 3 months blanking period (LR).

Results

Patients with ER compared to those without ER had significantly more LR (74.5% vs 16.5% vs, P < .001). The occurrence of ER during the first, second and third months showed increasing LR rates of 35.2%, 67.9%, and 94.8%, respectively (P < .001). Receiver operator characteristic analysis revealed a blanking period of 46 days with the highest sensitivity (68.1%) and specificity (96.5%). Later timing and longer time span of ER were independent predictors for LR in multivariable analysis.

Conclusion

ER is a strong predictor for LR. Our study advocates a shortening of the post-PVI blanking period followed by a ""gray zone"" up to 3 months where individualized therapeutic decisions based on additional risk factors should be considered. We suggest that the ER time span might serve as such a predictor identifying patients at the highest risk for LR.",,doi:https://doi.org/10.1111/jce.14368 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"

Background

Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.

Methods and findings

We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.

Conclusions and relevance

Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render 34348396,https://doi.org/10.1097/ede.0000000000001393,Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.,"Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",,"Epidemiology (Cambridge, Mass.)",2021,2021-09-01,Y,,,,"

Background

Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.

Methods

We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.

Results

Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.

Conclusion

Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",,doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render; html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx @@ -1312,8 +1315,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35115301,https://doi.org/10.1136/bjophthalmol-2021-319641,Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study.,"Gokhale KM, Adderley NJ, Subramanian A, Lee WH, Han D, Coker J, Braithwaite T, Denniston AK, Keane PA, Nirantharakumar K.",,The British journal of ophthalmology,2023,2022-02-03,N,Degeneration; epidemiology; Macula,,,"

Background

Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.

Aims

To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.

Methods

A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.

Results

A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.

Conclusion

We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.",,doi:https://doi.org/10.1136/bjophthalmol-2021-319641 33521535,https://doi.org/10.1136/bmjnph-2020-000107,Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index: an observational study of 335 046 UK Biobank participants.,"Mason KE, Palla L, Pearce N, Phelan J, Cummins S.",,"BMJ nutrition, prevention & health",2020,2020-10-05,Y,Malnutrition; Dietary Patterns,,,"

Background

There is growing recognition that recent global increases in obesity are the product of a complex interplay between genetic and environmental factors. However, in gene-environment studies of obesity, 'environment' usually refers to individual behavioural factors that influence energy balance, whereas more upstream environmental factors are overlooked. We examined gene-environment interactions between genetic risk of obesity and two neighbourhood characteristics likely to be associated with obesity (proximity to takeaway/fast-food outlets and availability of physical activity facilities).

Methods

We used data from 335 046 adults aged 40-70 in the UK Biobank cohort to conduct a population-based cross-sectional study of interactions between neighbourhood characteristics and genetic risk of obesity, in relation to body mass index (BMI). Proximity to a fast-food outlet was defined as distance from home address to nearest takeaway/fast-food outlet, and availability of physical activity facilities as the number of formal physical activity facilities within 1 km of home address. Genetic risk of obesity was operationalised by weighted Genetic Risk Scores of 91 or 69 single nucleotide polymorphisms (SNP), and by six individual SNPs considered separately. Multivariable, mixed-effects models with product terms for the gene-environment interactions were estimated.

Results

After accounting for likely confounding, the association between proximity to takeaway/fast-food outlets and BMI was stronger among those at increased genetic risk of obesity, with evidence of an interaction with polygenic risk scores (p=0.018 and p=0.028 for 69-SNP and 91-SNP scores, respectively) and in particular with a SNP linked to MC4R (p=0.009), a gene known to regulate food intake. We found very little evidence of gene-environment interaction for the availability of physical activity facilities.

Conclusions

Individuals at an increased genetic risk of obesity may be more sensitive to exposure to the local fast-food environment. Ensuring that neighbourhood residential environments are designed to promote a healthy weight may be particularly important for those with greater genetic susceptibility to obesity.",,doi:https://doi.org/10.1136/bmjnph-2020-000107; html:https://europepmc.org/articles/PMC7841812; pdf:https://europepmc.org/articles/PMC7841812?pdf=render 34939832,https://doi.org/10.1308/rcsann.2021.0206,"Projections for primary hip and knee replacement surgery up to the year 2060: an analysis based on data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.","Matharu GS, Culliford DJ, Blom AW, Judge A.",,Annals of the Royal College of Surgeons of England,2022,2021-12-23,N,Total hip replacement; Total Knee Replacement; Demand; Future Numbers,,,"

Introduction

We estimated the number of primary total hip and knee replacements (THR and TKR) that will need to be performed up to the year 2060.

Methods

We used data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man on the volume of primary THRs (n=94,936) and TKRs (n=100,547) performed in 2018. We projected future numbers of THR and TKR using a static estimated rate from 2018 applied to population growth forecast data from the UK Office for National Statistics up to 2060.

Results

By 2060, THR and TKR volume would increase from 2018 levels by an estimated 37.7% (n=130,766) and 36.6% (n=137,341), respectively. For both males and females demand for surgery was also higher for patients aged 70 and over, with older patients having the biggest relative increase in volume over time: 70-79 years (44.6% males, 41.2% females); 80-89 years (112.4% males, 85.6% females); 90 years and older (348.0% males, 198.2% females).

Conclusion

By 2060 demand for hip and knee joint replacement is estimated to increase by almost 40%. Demand will be greatest in older patients (70+ years), which will have significant implications for the health service requiring forward planning given that morbidity and resource use is higher in this population. These issues, coupled with two waves of COVID-19, will impact the ability of health services to deliver timely joint replacement to many patients for a number of years, requiring urgent planning.",,doi:https://doi.org/10.1308/rcsann.2021.0206; html:https://europepmc.org/articles/PMC9157920; pdf:https://europepmc.org/articles/PMC9157920?pdf=render; doi:https://doi.org/10.1308/rcsann.2021.0206 -34931349,https://doi.org/10.1111/bcp.15191,Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.,"Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.",,British journal of clinical pharmacology,2022,2022-01-28,Y,IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling,,,"

Aims

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

Methods

We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.

Results

A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.

Conclusions

IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.",,doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render +34931349,https://doi.org/10.1111/bcp.15191,Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.,"Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.",,British journal of clinical pharmacology,2022,2022-01-28,Y,IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling,,,"

Aims

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

Methods

We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.

Results

A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.

Conclusions

IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.",,doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render 33372068,https://doi.org/10.1136/bmjopen-2020-038324,Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.,"Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.",,BMJ open,2020,2020-12-28,Y,Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Introduction

Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods and analysis

We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics and dissemination

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero registration number

CRD42020163941.",,doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render 34155917,https://doi.org/10.1161/jaha.120.020246,Antenatal Exposure to UV-B Radiation and Preeclampsia: A Retrospective Cohort Study.,"Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, Megaw LJ, Smith GCS, Stock SJ, Dibben C, Pell JP.",,Journal of the American Heart Association,2021,2021-06-22,Y,UV light; Preeclampsia; Seasonal variations; Environmental Exposures,,,"Background Risk of preeclampsia varies by month of delivery. We tested whether this seasonal patterning may be mediated through maternal vitamin D concentration using antenatal exposure to UV-B radiation as an instrumental variable. Methods and Results Scottish maternity records were linked to antenatal UV-B exposure derived from satellites between 2000 and 2010. Logistic regression analyses were used to explore the association between UV-B and preeclampsia, adjusting for the potential confounding effects of month of conception, child's sex, gestation, parity, and mean monthly temperature. Of the 522 896 eligible singleton deliveries, 8689 (1.66%) mothers developed preeclampsia. Total antenatal UV-B exposure ranged from 43.18 to 101.11 kJ/m2 and was associated with reduced risk of preeclampsia with evidence of a dose-response relationship (highest quintile of exposure: adjusted odds ratio, 0.57; 95% CI, 0.44-0.72; P<0.001). Associations were demonstrated for UV-B exposure in all 3 trimesters. Conclusions The seasonal patterning of preeclampsia may be mediated through low maternal vitamin D concentration in winter resulting from low UV-B radiation. Interventional studies are required to determine whether vitamin D supplements or UV-B-emitting light boxes can reduce the seasonal patterning of preeclampsia.",,doi:https://doi.org/10.1161/JAHA.120.020246; html:https://europepmc.org/articles/PMC8403301; pdf:https://europepmc.org/articles/PMC8403301?pdf=render 36330526,https://doi.org/10.3389/fimmu.2022.1032331,Levels of soluble complement regulators predict severity of COVID-19 symptoms.,"Tierney AL, Alali WM, Scott T, Rees-Unwin KS, CITIID-NIHR BioResource COVID-19 Collaboration, Clark SJ, Unwin RD.",,Frontiers in immunology,2022,2022-10-18,Y,Complement; Mass spectrometry; Biomarkers; Factor H; Factor H-related Proteins; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.",,doi:https://doi.org/10.3389/fimmu.2022.1032331; html:https://europepmc.org/articles/PMC9624227; pdf:https://europepmc.org/articles/PMC9624227?pdf=render @@ -1325,28 +1328,28 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 31994239,https://doi.org/10.1002/bimj.201900041,Estimating treatment effects with partially observed covariates using outcome regression with missing indicators.,"Blake HA, Leyrat C, Mansfield KE, Tomlinson LA, Carpenter J, Williamson EJ.",,Biometrical journal. Biometrische Zeitschrift,2020,2020-01-29,N,Average Treatment Effect; Outcome Regression; Missing Covariate Data; Missing Indicator; Missing Confounder Data,,,"Missing data is a common issue in research using observational studies to investigate the effect of treatments on health outcomes. When missingness occurs only in the covariates, a simple approach is to use missing indicators to handle the partially observed covariates. The missing indicator approach has been criticized for giving biased results in outcome regression. However, recent papers have suggested that the missing indicator approach can provide unbiased results in propensity score analysis under certain assumptions. We consider assumptions under which the missing indicator approach can provide valid inferences, namely, (1) no unmeasured confounding within missingness patterns; either (2a) covariate values of patients with missing data were conditionally independent of treatment or (2b) these values were conditionally independent of outcome; and (3) the outcome model is correctly specified: specifically, the true outcome model does not include interactions between missing indicators and fully observed covariates. We prove that, under the assumptions above, the missing indicator approach with outcome regression can provide unbiased estimates of the average treatment effect. We use a simulation study to investigate the extent of bias in estimates of the treatment effect when the assumptions are violated and we illustrate our findings using data from electronic health records. In conclusion, the missing indicator approach can provide valid inferences for outcome regression, but the plausibility of its assumptions must first be considered carefully.",,doi:https://doi.org/10.1002/bimj.201900041 32846977,https://doi.org/10.3390/ijerph17176139,Agreement between the International Physical Activity Questionnaire and Accelerometry in Adults with Orthopaedic Injury. ,"Veitch WG, Climie RE, Gabbe BJ, Dunstan DW, Owen N, Ekegren CL.",,International journal of environmental research and public health,2020,2020-08-24,Y,,,,"Orthopaedic injury can lead to decreased physical activity. Valid measures for assessing physical activity are therefore needed in this population. The aim of this study was to determine the agreement and concordance between the International Physical Activity Questionnaire-Short Form (IPAQ) and device-measured physical activity and sitting time in orthopaedic injury patients. Adults with isolated upper or lower limb fracture (n = 46; mean age of 40.5 years) wore two activity monitors (ActiGraph wGT3X-BT and activPAL) for 10 days, from 2 weeks post-discharge. The IPAQ was also completed for a concurrent 7-day period. Lin's concordance correlation coefficients and Bland-Altman plots were calculated to compare walking/stepping time, total METmins, and sitting time. The IPAQ overestimated device-derived walking time (mean difference = 2.34 ± 7.33 h/week) and total METmins (mean difference = 767 ± 1659 METmins/week) and underestimated sitting time (mean difference = -2.26 ± 3.87 h/day). There was fair concordance between IPAQ-reported and device-measured walking (ρ = 0.34) and sitting time (ρ = 0.38) and moderate concordance between IPAQ-reported and device-measured METmins (ρ = 0.43). In patients with orthopaedic injury, the IPAQ overestimates physical activity and underestimates sitting time. Higher agreement was observed in the forms of activity (walking, total PA and sitting) commonly performed by this patient group.",,doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?pdf=render 33692568,https://doi.org/10.1038/s41588-021-00783-5,The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation.,"Lambert SA, Gil L, Jupp S, Ritchie SC, Xu Y, Buniello A, McMahon A, Abraham G, Chapman M, Parkinson H, Danesh J, MacArthur JAL, Inouye M.",,Nature genetics,2021,2021-04-01,N,,,,,,doi:https://doi.org/10.1038/s41588-021-00783-5 -36063293,https://doi.org/10.1186/s12348-022-00304-3,Evaluating patient-reported outcome measures (PROMs) for clinical trials and clinical practice in adult patients with uveitis or scleritis: a systematic review.,"O'Donovan C, Panthagani J, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston A, Moore D, Braithwaite T.",,Journal of ophthalmic inflammation and infection,2022,2022-09-05,Y,,,,"Patient reported outcome measures (PROMs) capture impact of disease and treatment on quality of life, and have an emerging role in clinical trial outcome measurement. This study included a systematic review and quality appraisal of PROMs developed or validated for use in adults with uveitis or scleritis. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and grey literature sources, to 5 November 2021. We used established quality criteria to grade each PROM instrument in multiple domains from A (high quality) to C (low quality), and assessed content development, validity, reliability and responsiveness. For instruments developed using classic test theory-based psychometric approaches, we assessed acceptability, item targeting and internal consistency. For instruments developed using Item Response Theory (IRT) (e.g. Rasch analysis), we assessed response categories, dimensionality, measurement precision, item fit statistics, differential item functioning and targeting. We identified and appraised four instruments applicable to certain uveitis types, but none for scleritis. Specifically, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ), a 3-part PROM for Birdshot retinochoroiditis (Birdshot Disease & Medication Symptoms Questionnaire [BD&MSQ], the quality of life (QoL) impact of Birdshot Chorioretinopathy [QoL BCR], and the QoL impact of BCR medication [QoL Meds], the Kings Sarcoidosis Questionnaire (KSQ), and a PROM for cytomegalovirus retinitis. These instruments had limited coverage for these heterogeneous conditions, with a focus on very rare subtypes. Psychometric appraisal revealed considerable variability between instruments, limited content development, and only one developed using Item Response Theory. In conclusion, there are few validated PROMs for patients with uveitis and none for scleritis, and existing instruments have suboptimal psychometric performance. We articulate why we do not recommend their inclusion as clinical trial outcome measures for drug licensing purposes, and highlight an unmet need for PROMs applicable to uveitis and scleritis.",,doi:https://doi.org/10.1186/s12348-022-00304-3; html:https://europepmc.org/articles/PMC9443634; pdf:https://europepmc.org/articles/PMC9443634?pdf=render 31446403,https://doi.org/10.1136/bmjopen-2018-026677,Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements.,"Li Q, Li X, Wang J, Liu H, Kwong JS, Chen H, Li L, Chung SC, Shah A, Chen Y, An Z, Sun X, Hemingway H, Tian H, Li S.",,BMJ open,2019,2019-08-24,Y,Gout; Hyperuricemia; Systematic review; Clinical Practice Guideline,,,"

Objectives

Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia.

Design

Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology.

Data sources

PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017).

Eligibility criteria

We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese.

Data extraction and synthesis

Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid.

Results

Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%-100.0%) and clarity of presentation (median 79.2%, range 48.6%-98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%-66.7%) and editorial independence (median 28.1%, range 0.0%-83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia.

Conclusions

Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies.

Prospero registration number

CRD42016046104.",,doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render +36063293,https://doi.org/10.1186/s12348-022-00304-3,Evaluating patient-reported outcome measures (PROMs) for clinical trials and clinical practice in adult patients with uveitis or scleritis: a systematic review.,"O'Donovan C, Panthagani J, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston A, Moore D, Braithwaite T.",,Journal of ophthalmic inflammation and infection,2022,2022-09-05,Y,,,,"Patient reported outcome measures (PROMs) capture impact of disease and treatment on quality of life, and have an emerging role in clinical trial outcome measurement. This study included a systematic review and quality appraisal of PROMs developed or validated for use in adults with uveitis or scleritis. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and grey literature sources, to 5 November 2021. We used established quality criteria to grade each PROM instrument in multiple domains from A (high quality) to C (low quality), and assessed content development, validity, reliability and responsiveness. For instruments developed using classic test theory-based psychometric approaches, we assessed acceptability, item targeting and internal consistency. For instruments developed using Item Response Theory (IRT) (e.g. Rasch analysis), we assessed response categories, dimensionality, measurement precision, item fit statistics, differential item functioning and targeting. We identified and appraised four instruments applicable to certain uveitis types, but none for scleritis. Specifically, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ), a 3-part PROM for Birdshot retinochoroiditis (Birdshot Disease & Medication Symptoms Questionnaire [BD&MSQ], the quality of life (QoL) impact of Birdshot Chorioretinopathy [QoL BCR], and the QoL impact of BCR medication [QoL Meds], the Kings Sarcoidosis Questionnaire (KSQ), and a PROM for cytomegalovirus retinitis. These instruments had limited coverage for these heterogeneous conditions, with a focus on very rare subtypes. Psychometric appraisal revealed considerable variability between instruments, limited content development, and only one developed using Item Response Theory. In conclusion, there are few validated PROMs for patients with uveitis and none for scleritis, and existing instruments have suboptimal psychometric performance. We articulate why we do not recommend their inclusion as clinical trial outcome measures for drug licensing purposes, and highlight an unmet need for PROMs applicable to uveitis and scleritis.",,doi:https://doi.org/10.1186/s12348-022-00304-3; html:https://europepmc.org/articles/PMC9443634; pdf:https://europepmc.org/articles/PMC9443634?pdf=render 31409800,https://doi.org/10.1038/s41467-019-11451-y,GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits.,"Pazoki R, Evangelou E, Mosen-Ansorena D, Pinto RC, Karaman I, Blakeley P, Gill D, Zuber V, Elliott P, Tzoulaki I, Dehghan A.",,Nature communications,2019,2019-08-13,Y,,Understanding the Causes of Disease,,"Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.",,doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render 37025302,https://doi.org/10.1093/jacamr/dlad039,Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis.,"Brankin AE, Fowler PW.",,JAC-antimicrobial resistance,2023,2023-04-04,Y,,,,"

Objectives

Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.

Methods

We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.

Results

Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.

Conclusions

Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.",,doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render 34750571,https://doi.org/10.1038/s42255-021-00478-5,Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases.,"Ritchie SC, Lambert SA, Arnold M, Teo SM, Lim S, Scepanovic P, Marten J, Zahid S, Chaffin M, Liu Y, Abraham G, Ouwehand WH, Roberts DJ, Watkins NA, Drew BG, Calkin AC, Di Angelantonio E, Soranzo N, Burgess S, Chapman M, Kathiresan S, Khera AV, Danesh J, Butterworth AS, Inouye M.",,Nature metabolism,2021,2021-11-08,Y,,,,"Cardiometabolic diseases are frequently polygenic in architecture, comprising a large number of risk alleles with small effects spread across the genome1-3. Polygenic scores (PGS) aggregate these into a metric representing an individual's genetic predisposition to disease. PGS have shown promise for early risk prediction4-7 and there is an open question as to whether PGS can also be used to understand disease biology8. Here, we demonstrate that cardiometabolic disease PGS can be used to elucidate the proteins underlying disease pathogenesis. In 3,087 healthy individuals, we found that PGS for coronary artery disease, type 2 diabetes, chronic kidney disease and ischaemic stroke are associated with the levels of 49 plasma proteins. Associations were polygenic in architecture, largely independent of cis and trans protein quantitative trait loci and present for proteins without quantitative trait loci. Over a follow-up of 7.7 years, 28 of these proteins associated with future myocardial infarction or type 2 diabetes events, 16 of which were mediators between polygenic risk and incident disease. Twelve of these were druggable targets with therapeutic potential. Our results demonstrate the potential for PGS to uncover causal disease biology and targets with therapeutic potential, including those that may be missed by approaches utilizing information at a single locus.",,doi:https://doi.org/10.1038/s42255-021-00478-5; html:https://europepmc.org/articles/PMC8574944; pdf:https://europepmc.org/articles/PMC8574944?pdf=render 31408247,https://doi.org/10.1002/hpja.287,An assessment of program evaluation methods and quality in Australian prevention agencies.,"Schwarzman J, Nau T, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Health promotion journal of Australia : official journal of Australian Association of Health Promotion Professionals,2020,2019-08-13,N,Program Evaluation; Government; Primary Prevention; Health Promotion; Evidence-based Practice; Health Equity; Non-government Organisations,,,"

Issue addressed

This study aimed to examine evaluation methods and quality in Australian health promotion agencies and the factors associated with this. The evidence base for prevention strategies is limited, with the evidence generated through program evaluation by health promotion and disease prevention agencies lacking rigour. Despite the need to improve the quality of evaluation, there is limited evidence of what influences evaluation quality in the prevention field.

Methods

Data were collected using the Evaluation Practice Analysis Survey and an audit and appraisal of evaluation reports. Descriptive analysis was used to examine evaluation characteristics and multivariable regression was used to explore the association between evaluation and organisational attributes and evaluation quality.

Results

In total, 392 evaluation reports were reviewed from 78 government and non-government agencies. Process evaluation was conducted most frequently, followed by impact evaluation. Overall evaluation quality was low (median 24.5%). In multivariable regression analysis, only two factors were associated with evaluation quality: health promotion budget (ratio of geometric means 1.53 [95% CI 1.02-2.29]); and, conducting statewide or national prevention programs (1.38 [95% CI 1.05-1.82]).

Conclusions

The findings show that the potential to improve evaluation quality is greatest in smaller organisations that deliver health promotion at a local or regional scale. SO WHAT?: By improving the rigour of existing evaluation, there is opportunity to build the evidence base for prevention strategies, which highlights the importance of embedding the enablers of program learning and evidence generation within health promotion and prevention organisations.",,doi:https://doi.org/10.1002/hpja.287 36343994,https://doi.org/10.1136/bmjopen-2022-063159,"Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.","Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",,BMJ open,2022,2022-11-07,Y,Infection control; epidemiology; Public Health; Covid-19,,,"

Objective

Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.

Design/setting/participants

HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.

Results

Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).

Conclusions

The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",,doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render 34425897,https://doi.org/10.1186/s13326-021-00249-x,Linking common human diseases to their phenotypes; development of a resource for human phenomics.,"Kafkas Ş, Althubaiti S, Gkoutos GV, Hoehndorf R, Schofield PN.",,Journal of biomedical semantics,2021,2021-08-23,Y,Ontologies; Text Mining; Uk Biobank; Disease–phenotype Associations,,,"

Background

In recent years a large volume of clinical genomics data has become available due to rapid advances in sequencing technologies. Efficient exploitation of this genomics data requires linkage to patient phenotype profiles. Current resources providing disease-phenotype associations are not comprehensive, and they often do not have broad coverage of the disease terminologies, particularly ICD-10, which is still the primary terminology used in clinical settings.

Methods

We developed two approaches to gather disease-phenotype associations. First, we used a text mining method that utilizes semantic relations in phenotype ontologies, and applies statistical methods to extract associations between diseases in ICD-10 and phenotype ontology classes from the literature. Second, we developed a semi-automatic way to collect ICD-10-phenotype associations from existing resources containing known relationships.

Results

We generated four datasets. Two of them are independent datasets linking diseases to their phenotypes based on text mining and semi-automatic strategies. The remaining two datasets are generated from these datasets and cover a subset of ICD-10 classes of common diseases contained in UK Biobank. We extensively validated our text mined and semi-automatically curated datasets by: comparing them against an expert-curated validation dataset containing disease-phenotype associations, measuring their similarity to disease-phenotype associations found in public databases, and assessing how well they could be used to recover gene-disease associations using phenotype similarity.

Conclusion

We find that our text mining method can produce phenotype annotations of diseases that are correct but often too general to have significant information content, or too specific to accurately reflect the typical manifestations of the sporadic disease. On the other hand, the datasets generated from integrating multiple knowledgebases are more complete (i.e., cover more of the required phenotype annotations for a given disease). We make all data freely available at https://doi.org/10.5281/zenodo.4726713 .",,doi:https://doi.org/10.1186/s13326-021-00249-x; html:https://europepmc.org/articles/PMC8383460; pdf:https://europepmc.org/articles/PMC8383460?pdf=render -36351458,https://doi.org/10.1016/s0140-6736(22)02074-8,Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.,"Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.",,"Lancet (London, England)",2022,2022-11-06,Y,,,,"

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.",,doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836 -33559289,https://doi.org/10.1002/ejp.1750,The association between exposure to domestic abuse in women and the development of syndromes indicating central nervous system sensitization: A retrospective cohort study using UK primary care records.,"Chandan JS, Keerthy D, Gokhale KM, Bradbury-Jones C, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,"European journal of pain (London, England)",2021,2021-03-15,N,,,,"

Background

Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations.

Methods

A retrospective cohort study using the 'The Health Improvement Network,' (UK primary care medical records) between 1st January 1995-31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow-up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health.

Results

During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85-2.80), chronic headaches (aIRR 3.15; 95% CI 1.07-9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25-1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44-2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14-1.93), vulvodynia (aIRR 0.42; 95% CI 0.14-1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28-3.61).

Conclusion

This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse.

Significance

Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences.",,doi:https://doi.org/10.1002/ejp.1750; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750 31479767,https://doi.org/10.1016/j.jaip.2019.08.030,Atopic Eczema in Adulthood and Risk of Depression and Anxiety: A Population-Based Cohort Study.,"Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, Langan SM.",,The journal of allergy and clinical immunology. In practice,2020,2019-08-31,Y,Depression; Anxiety; Atopic Eczema; Atopic Dermatitis; Severity; Population-based,Understanding the Causes of Disease,,"

Background

Atopic eczema is a common and debilitating condition associated with depression and anxiety, but the nature of this association remains unclear.

Objective

To explore the temporal relationship between atopic eczema and new depression/anxiety.

Methods

This matched cohort study used routinely collected data from the UK Clinical Practice Research Datalink, linked to hospital admissions data. We identified adults with atopic eczema (1998-2016) using a validated algorithm, and up to 5 individuals without atopic eczema matched on date of diagnosis, age, sex, and general practice. We estimated the hazard ratio (HR) for new depression/anxiety using stratified Cox regression to account for age, sex, calendar period, Index of Multiple Deprivation, glucocorticoid treatment, obesity, smoking, and harmful alcohol use.

Results

We identified 526,808 adults with atopic eczema who were matched to 2,569,030 without. Atopic eczema was associated with increased incidence of new depression (HR, 1.14; 99% CI, 1.12-1.16) and anxiety (HR, 1.17; 99% CI, 1.14-1.19). We observed a stronger effect of atopic eczema on depression with increasing atopic eczema severity (HR [99% CI] compared with no atopic eczema: mild, 1.10 [1.08-1.13]; moderate, 1.19 [1.15-1.23]; and severe, 1.26 [1.17-1.37]). A dose-response association, however, was less apparent for new anxiety diagnosis (HR [99% CI] compared with no atopic eczema: mild, 1.14 [1.11-1.18]; moderate, 1.21 [1.17-1.26]; and severe, 1.15; [1.05-1.25]).

Conclusions

Adults with atopic eczema are more likely to develop new depression and anxiety. For depression, we observed a dose-response relationship with atopic eczema severity.",,doi:https://doi.org/10.1016/j.jaip.2019.08.030; html:https://europepmc.org/articles/PMC6947493; pdf:https://europepmc.org/articles/PMC6947493?pdf=render +33559289,https://doi.org/10.1002/ejp.1750,The association between exposure to domestic abuse in women and the development of syndromes indicating central nervous system sensitization: A retrospective cohort study using UK primary care records.,"Chandan JS, Keerthy D, Gokhale KM, Bradbury-Jones C, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,"European journal of pain (London, England)",2021,2021-03-15,N,,,,"

Background

Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations.

Methods

A retrospective cohort study using the 'The Health Improvement Network,' (UK primary care medical records) between 1st January 1995-31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow-up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health.

Results

During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85-2.80), chronic headaches (aIRR 3.15; 95% CI 1.07-9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25-1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44-2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14-1.93), vulvodynia (aIRR 0.42; 95% CI 0.14-1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28-3.61).

Conclusion

This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse.

Significance

Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences.",,doi:https://doi.org/10.1002/ejp.1750; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750 +36351458,https://doi.org/10.1016/s0140-6736(22)02074-8,Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.,"Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.",,"Lancet (London, England)",2022,2022-11-06,Y,,,,"

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.",,doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836 32400358,https://doi.org/10.2807/1560-7917.es.2020.25.18.2000632,"Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020.","Jit M, Jombart T, Nightingale ES, Endo A, Abbott S, LSHTM Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Edmunds WJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-05-01,Y,Surveillance; intensive care unit; mathematical model; Reproduction Number; Sars-cov-2; Coronavirus Disease 2019,,,"An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000-173,000) new cases and 258 (95% CrI: 220-319) new critical care reports, with 527,000 (95% CrI: 362,000-797,000) cumulative cases since 16 February.","The authors of this paper estimate the number of cases and spread of COVID-19 using data on critical care admissions within the UK, from a period of February to March 2020. Their results suggest that the UK had hundreds of thousands of COVID-19 cases by the time the national lockdown was implemented. They highlight the usefulness of surveilling critical care data to better understand the dynamics of the epidemic and better inform the response measures.",doi:https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000632; html:https://europepmc.org/articles/PMC7219029; pdf:https://europepmc.org/articles/PMC7219029?pdf=render -35967893,https://doi.org/10.1080/20008066.2022.2105577,Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.,"Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,European journal of psychotraumatology,2022,2022-08-09,Y,Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19,,,"Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.",,doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render 33591566,https://doi.org/10.1007/s43441-021-00263-2,Advancing UK Regulatory Science Strategy in the Context of Global Regulation: a Stakeholder Survey.,"Cruz Rivera S, Torlinska B, Marston E, Denniston AK, Oliver K, Hoare S, Calvert MJ.",,Therapeutic innovation & regulatory science,2021,2021-02-16,Y,Regulatory Science; Health Products; Medicines And Devices,,,"

Background

The UK's transition from the European Union creates both an urgent need and key opportunity for the UK and its global collaborators to consider new approaches to the regulation of emerging technologies, underpinned by regulatory science. This survey aimed to identify the most accurate definition of regulatory science, to define strategic areas of the regulation of healthcare innovation which can be informed through regulatory science and to explore the training and infrastructure needed to advance UK and international regulatory science.

Methods

A survey was distributed to UK healthcare professionals, academics, patients, health technology assessment agencies, ethicists and trade associations, as well as international regulators, pharmaceutical companies and small or medium enterprises which have expertise in regulatory science and in developing or applying regulation in healthcare. Subsequently, a descriptive quantitative analyses of survey results and directed thematic analysis of free-text comments were applied.

Results

Priority areas for UK regulatory science identified by 145 participants included the following: flexibility: the capability of regulations to adapt to novel products and target patient outcomes; co-development: collaboration across sectors, e.g. patients, manufacturers, regulators, and educators working together to develop appropriate training for novel product deployment; responsiveness: the preparation of frameworks which enable timely innovation required by emerging events; speed: the rate at which new products can reach the market; reimbursement: developing effective tools to track and evaluate outcomes for ""pay for performance"" products; and education and professional development.

Conclusions

The UK has a time-critical opportunity to establish its national and international strategy for regulatory science leadership by harnessing broader academic input, developing strategic cross-sector collaborations, incorporating patients' experiences and perspectives, and investing in a skilled workforce.",,doi:https://doi.org/10.1007/s43441-021-00263-2; html:https://europepmc.org/articles/PMC7885762; pdf:https://europepmc.org/articles/PMC7885762?pdf=render +35967893,https://doi.org/10.1080/20008066.2022.2105577,Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.,"Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,European journal of psychotraumatology,2022,2022-08-09,Y,Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19,,,"Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.",,doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render 31282950,https://doi.org/10.1001/jamaneurol.2019.1812,Association Between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom.,"Adderley NJ, Subramanian A, Nirantharakumar K, Yiangou A, Gokhale KM, Mollan SP, Sinclair AJ.",,JAMA neurology,2019,2019-09-01,Y,,Understanding the Causes of Disease,,"

Importance

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).

Objectives

To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH.

Design, setting, and participants

This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27 125) by BMI and age.

Main outcomes and measures

Adjusted hazard ratios (aHRs) of cardiovascular outcomes were calculated using Cox regression models. The primary outcome was a composite of any CVD (heart failure, ischemic heart disease, and stroke/TIA), and the secondary outcomes were each CVD outcome, type 2 diabetes, and hypertension.

Results

In total, 2760 women with IIH and 27 125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P < .001); heart failure, 1.97 (95% CI, 1.16-3.37; P = .01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P = .002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P < .001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P = .009); and hypertension, 1.55 (95% CI, 1.30-1.84; P < .001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100 000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100 000 women. Incidence increased markedly with BMI higher than 30.

Conclusions and relevance

Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in CVD risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.",,doi:https://doi.org/10.1001/jamaneurol.2019.1812; html:https://europepmc.org/articles/PMC6618853 34954079,https://doi.org/10.1016/j.jnutbio.2021.108929,Iron-mediated epigenetic activation of NRF2 targets.,"Horniblow RD, Pathak P, Balacco DL, Acharjee A, Lles E, Gkoutos G, Beggs AD, Tselepis C.",,The Journal of nutritional biochemistry,2022,2021-12-23,N,Iron; Diet; Oxidative stress; NRF2; Epigenome; Nutrigenetics; Hypomethylation,,,"The toxic effects of excess dietary iron within the colonic lumen are well documented, particularly in the context of Inflammatory Bowel Disease (IBD) and Colorectal Cancer (CRC). Proposed mechanisms that underpin iron-associated intestinal disease include: (1) the pro-inflammatory and ROS-promoting nature of iron, (2) gene-expression alterations, and (3) intestinal microbial dysbiosis. However, to date no studies have examined the effect of iron on the colonic epigenome. Here we demonstrate that chronic iron exposure of colonocytes leads to significant hypomethylation of the epigenome. Bioinformatic analysis highlights a significant epigenetic effect on NRF2 (nuclear factor erythroid 2-related factor 2) pathway targets (including NAD(P)H Quinone Dehydrogenase 1 [NQO1] and Glutathione peroxidase 2 [GPX2]); this demethylating effect was validated and subsequent gene and protein expression quantified. These epigenetic modifications were not observed upon the diminishment of cellular lipid peroxidation with endogenous glutathione and the subsequent removal of iron. Additionally, the induction of TET1 expression was found post-iron treatment, highlighting the possibility of an oxidative-stress induction of TET1 and subsequent hypomethylation of NRF2 targets. In addition, a strong time dependence on the establishment of iron-orchestrated hypomethylation was found which was concurrent with the increase in the intracellular labile iron pool (LIP) and lipid peroxidation levels. These epigenetic changes were further validated in murine intestinal mucosa in models administered a chronic iron diet, providing evidence for the likelihood of dietary-iron mediated epigenetic alterations in vivo. Furthermore, significant correlations were found between NQO1 and GPX2 demethylation and human intestinal tissue iron-status, thus suggesting that these iron-mediated epigenetic modifications are likely in iron-replete enterocytes. Together, these data describe a novel mechanism by which excess dietary iron is able to alter the intestinal phenotype, which could have implications in iron-mediated intestinal disease and the regulation of ferroptosis.",,doi:https://doi.org/10.1016/j.jnutbio.2021.108929 35244709,https://doi.org/10.1093/europace/euac022,Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.,"Wilkinson C, Wu J, Clegg A, Nadarajah R, Rockwood K, Todd O, Gale CP.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-07-01,Y,Bleeding; Atrial fibrillation; Stroke; Frailty; Outcome; Oral Anticoagulation; Oral Anticoagulation Prescription,,,"

Aims

People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF.

Methods and results

Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64-0.75, direct oral anticoagulant (DOAC) 0.42, 0.33-0.53; mild frailty: VKA 0.52, 0.50-0.54, DOAC 0.57, 0.52-0.63; moderate: VKA 0.54, 0.52-0.56, DOAC 0.57, 0.52-0.63; severe: VKA 0.48, 0.45-0.51, DOAC 0.58, 0.52-0.65], with cumulative incidence function effects greater for DOAC than VKA.

Conclusion

Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.",,doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render 36082306,https://doi.org/10.1016/j.xgen.2021.100004,Workshop proceedings: GWAS summary statistics standards and sharing.,"MacArthur JAL, Buniello A, Harris LW, Hayhurst J, McMahon A, Sollis E, Cerezo M, Hall P, Lewis E, Whetzel PL, Bahcall OG, Barroso I, Carroll RJ, Inouye M, Manolio TA, Rich SS, Hindorff LA, Wiley K, Parkinson H.",,Cell genomics,2021,2021-10-01,Y,,,,"Genome-wide association studies (GWASs) have enabled robust mapping of complex traits in humans. The open sharing of GWAS summary statistics (SumStats) is essential in facilitating the larger meta-analyses needed for increased power in resolving the genetic basis of disease. However, most GWAS SumStats are not readily accessible because of limited sharing and a lack of defined standards. With the aim of increasing the availability, quality, and utility of GWAS SumStats, the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) GWAS Catalog organized a community workshop to address the standards, infrastructure, and incentives required to promote and enable sharing. We evaluated the barriers to SumStats sharing, both technological and sociological, and developed an action plan to address those challenges and ensure that SumStats and study metadata are findable, accessible, interoperable, and reusable (FAIR). We encourage early deposition of datasets in the GWAS Catalog as the recognized central repository. We recommend standard requirements for reporting elements and formats for SumStats and accompanying metadata as guidelines for community standards and a basis for submission to the GWAS Catalog. Finally, we provide recommendations to enable, promote, and incentivize broader data sharing, standards and FAIRness in order to advance genomic medicine.",,doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?pdf=render 34756707,https://doi.org/10.1016/j.evalprogplan.2021.102019,"How practitioner, organisational and system-level factors act to influence health promotion evaluation capacity: Validation of a conceptual framework.","Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2022,2021-10-20,N,Path analysis; Primary Prevention; Health Promotion; Confirmatory Factor Analysis; Evaluation Capacity,,,"The need to improve the practice and quality of evaluation in the health promotion and disease prevention field is widely recognised. In order to plan, implement and evaluate health promotion evaluation capacity building efforts, there is a need to better understand the practitioner, organisational and system-level determinants of evaluation capacity and practice. This study aimed to assess the validity Evaluation Practice Analysis Survey (EPAS) constructs using confirmatory factor analysis and validate a conceptual framework of health promotion evaluation capacity using path analysis. Experienced Australian health promotion practitioners completed the survey (n = 219). Twenty-one of the original 23 EPAS scales were assessed as reliable and valid. The final model was found to have good fit (χ214 = 18.72, p = 0.18, root mean square error of approximation = 0.04, 90% CI 0.00-0.82, Comparative Fit Index = 1.00, standardised root mean square residual = 0.04). This model supports the role of the organisation in facilitating evaluation practice through leadership, culture, systems, support and resources. It builds on existing frameworks from other fields to incorporate political, funding and administrative factors. This study provides an evidence-based model of evaluation capacity that organisations, funders and policy makers can use to plan and implement more effective evaluation capacity building strategies within organisations and the wider prevention field.",,doi:https://doi.org/10.1016/j.evalprogplan.2021.102019 32743489,https://doi.org/10.1016/j.eclinm.2020.100469,Gender differences in the presentation of fibromyalgia amongst children who have been maltreated.,"Chandan JS, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,EClinicalMedicine,2020,2020-07-23,Y,,,,,,doi:https://doi.org/10.1016/j.eclinm.2020.100469; html:https://europepmc.org/articles/PMC7385442; pdf:https://europepmc.org/articles/PMC7385442?pdf=render -37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 33615277,https://doi.org/10.1016/j.xpro.2021.100334,Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes.,"Maas RGC, Lee S, Harakalova M, Snijders Blok CJB, Goodyer WR, Hjortnaes J, Doevendans PAFM, Van Laake LW, van der Velden J, Asselbergs FW, Wu JC, Sluijter JPG, Wu SM, Buikema JW.",,STAR protocols,2021,2021-02-09,Y,Cell differentiation; Cell culture; Stem Cells,,,"Since the discovery of human induced pluripotent stem cells (hiPSCs), numerous strategies have been established to efficiently derive cardiomyocytes from hiPSCs (hiPSC-CMs). Here, we describe a cost-effective strategy for the subsequent massive expansion (>250-fold) of high-purity hiPSC-CMs relying on two aspects: removal of cell-cell contacts and small-molecule inhibition with CHIR99021. The protocol maintains CM functionality, allows cryopreservation, and the cells can be used in downstream assays such as disease modeling, drug and toxicity screening, and cell therapy. For complete details on the use and execution of this protocol, please refer to Buikema (2020).",,doi:https://doi.org/10.1016/j.xpro.2021.100334; html:https://europepmc.org/articles/PMC7881265; pdf:https://europepmc.org/articles/PMC7881265?pdf=render +37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 36545235,https://doi.org/10.1177/26335565221145493,The DynAIRx Project Protocol: Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity.,"Walker LE, Abuzour AS, Bollegala D, Clegg A, Gabbay M, Griffiths A, Kullu C, Leeming G, Mair FS, Maskell S, Relton S, Ruddle RA, Shantsila E, Sperrin M, Van Staa T, Woodall A, Buchan I.",,Journal of multimorbidity and comorbidity,2022,2022-01-01,Y,Artificial intelligence; Frailty; Mental health; Polypharmacy; Multimorbidity; Medicines Optimisation,,,"

Background

Structured Medication Reviews (SMRs) are intended to help deliver the NHS Long Term Plan for medicines optimisation in people living with multiple long-term conditions and polypharmacy. It is challenging to gather the information needed for these reviews due to poor integration of health records across providers and there is little guidance on how to identify those patients most urgently requiring review.

Objective

To extract information from scattered clinical records on how health and medications change over time, apply interpretable artificial intelligence (AI) approaches to predict risks of poor outcomes and overlay this information on care records to inform SMRs. We will pilot this approach in primary care prescribing audit and feedback systems, and co-design future medicines optimisation decision support systems.

Design

DynAIRx will target potentially problematic polypharmacy in three key multimorbidity groups, namely, people with (a) mental and physical health problems, (b) four or more long-term conditions taking ten or more drugs and (c) older age and frailty. Structured clinical data will be drawn from integrated care records (general practice, hospital, and social care) covering an ∼11m population supplemented with Natural Language Processing (NLP) of unstructured clinical text. AI systems will be trained to identify patterns of conditions, medications, tests, and clinical contacts preceding adverse events in order to identify individuals who might benefit most from an SMR.

Discussion

By implementing and evaluating an AI-augmented visualisation of care records in an existing prescribing audit and feedback system we will create a learning system for medicines optimisation, co-designed throughout with end-users and patients.",,doi:https://doi.org/10.1177/26335565221145493; html:https://europepmc.org/articles/PMC9761229; pdf:https://europepmc.org/articles/PMC9761229?pdf=render 34970633,https://doi.org/10.23889/ijpds.v6i1.1674,Evaluation of the ASSIGN open-source deterministic address-matching algorithm for allocating unique property reference numbers to general practitioner-recorded patient addresses.,"Harper G, Stables D, Simon P, Ahmed Z, Smith K, Robson J, Dezateux C.",,International journal of population data science,2021,2021-12-08,Y,Quality assurance; Data Linkage; Population Health; Electronic Health Record; Addresses; Address-matching; Place-based Health,,,"

Introduction

Linking places to people is a core element of the UK government's geospatial strategy. Matching patient addresses in electronic health records to their Unique Property Reference Numbers (UPRNs) enables spatial linkage for research, innovation and public benefit. Available algorithms are not transparent or evaluated for use with addresses recorded by health care providers.

Objectives

To describe and quality assure the open-source deterministic ASSIGN address-matching algorithm applied to general practitioner-recorded patient addresses.

Methods

Best practice standards were used to report the ASSIGN algorithm match rate, sensitivity and positive predictive value using gold-standard datasets from London and Wales. We applied the ASSIGN algorithm to the recorded addresses of a sample of 1,757,018 patients registered with all general practices in north east London. We examined bias in match results for the study population using multivariable analyses to estimate the likelihood of an address-matched UPRN by demographic, registration, and organisational variables.

Results

We found a 99.5% and 99.6% match rate with high sensitivity (0.999,0.998) and positive predictive value (0.996,0.998) for the Welsh and London gold standard datasets respectively, and a 98.6% match rate for the study population.The 1.4% of the study population without a UPRN match were more likely to have changed registered address in the last 12 months (match rate: 95.4%), be from a Chinese ethnic background (95.5%), or registered with a general practice using the SystmOne clinical record system (94.4%). Conversely, people registered for more than 6.5 years with their general practitioner were more likely to have a match (99.4%) than those with shorter registration durations.

Conclusions

ASSIGN is a highly accurate open-source address-matching algorithm with a high match rate and minimal biases when evaluated against a large sample of general practice-recorded patient addresses. ASSIGN has potential to be used in other address-based datasets including those with information relevant to the wider determinants of health.",,doi:https://doi.org/10.23889/ijpds.v6i1.1674; html:https://europepmc.org/articles/PMC8678979; pdf:https://europepmc.org/articles/PMC8678979?pdf=render 33653287,https://doi.org/10.1186/s12875-021-01384-1,"A cross-sectional study reporting concussion exposure, assessment and management in Western Australian general practice.","Thomas E, Chih H, Gabbe B, Fitzgerald M, Cowen G.",,BMC family practice,2021,2021-03-02,Y,,,,"

Background

General Practitioners (GPs) may be called upon to assess patients who have sustained a concussion despite limited information being available at this assessment. Information relating to how concussion is actually being assessed and managed in General Practice is scarce. This study aimed to identify characteristics of current Western Australian (WA) GP exposure to patients with concussion, factors associated with GPs' knowledge of concussion, confidence of GPs in diagnosing and managing patients with concussion, typical referral practices and familiarity of GPs with guidelines.

Methods

In this cross-sectional study, GPs in WA were recruited via the RACGP WA newsletter and shareGP and the consented GPs completed an electronic survey. Associations were performed using Chi-squared tests or Fisher's Exact test.

Results

Sixty-six GPs in WA responded to the survey (response rate = 1.7%). Demographics, usual practice, knowledge, confidence, identification of prolonged recovery as well as guideline and resource awareness of GPs who practised in regional and metropolitan areas were comparable (p > 0.05). Characteristics of GPs were similar between those who identified all symptoms of concussion and distractors correctly and those who did not (p > 0.05). However, 84% of the respondents who had never heard of concussion guidelines were less likely to answer all symptoms and distractors correctly (p = 0.039). Whilst 78% of the GPs who were confident in their diagnoses had heard of guidelines (p = 0.029), confidence in managing concussion was not significantly associated with GPs exposure to guidelines. It should be noted that none of the respondents correctly identified signs of concussion and excluded the distractors.

Conclusions

Knowledge surrounding concussion guidelines, diagnosis and management varied across GPs in WA. Promotion of available concussion guidelines may assist GPs who lack confidence in making a diagnosis. The lack of association between GPs exposure to guidelines and confidence managing concussion highlights that concussion management may be an area where GPs could benefit from additional education and support.",,doi:https://doi.org/10.1186/s12875-021-01384-1; html:https://europepmc.org/articles/PMC7927406; pdf:https://europepmc.org/articles/PMC7927406?pdf=render @@ -1356,10 +1359,9 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34596018,https://doi.org/10.2807/1560-7917.es.2021.26.39.2001440,"Strategies to reduce the risk of SARS-CoV-2 importation from international travellers: modelling estimations for the United Kingdom, July 2020. ","Clifford S, Quilty BJ, Russell TW, Liu Y, Chan YD, Pearson CAB, Eggo RM, Endo A, CMMID COVID-19 Working Group, Flasche S, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-09-01,Y,,,,"BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.",,doi:https://doi.org/10.2807/1560-7917.ES.2021.26.39.2001440; html:https://europepmc.org/articles/PMC8485583; pdf:https://europepmc.org/articles/PMC8485583?pdf=render 34980174,https://doi.org/10.1186/s12967-021-03210-9,"Increased burden of cardiovascular disease in people with liver disease: unequal geographical variations, risk factors and excess years of life lost.","Chang WH, Mueller SH, Chung SC, Foster GR, Lai AG.",,Journal of translational medicine,2022,2022-01-03,Y,liver disease; Geographical variations; incidence; Cardiovascular Risk; Electronic Health Records; Years Of Life Lost,,,"

Background

People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.

Methods

We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD).

Results

The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50-59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages.

Conclusions

We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment.",,doi:https://doi.org/10.1186/s12967-021-03210-9; html:https://europepmc.org/articles/PMC8722174; pdf:https://europepmc.org/articles/PMC8722174?pdf=render 32735830,https://doi.org/10.1016/s2352-3026(20)30228-3,Cardiovascular adverse events following treatment for non-Hodgkin lymphoma - Authors' reply.,"Linschoten M, Kamphuis JA, Asselbergs FW.",,The Lancet. Haematology,2020,2020-08-01,N,,,,,,doi:https://doi.org/10.1016/S2352-3026(20)30228-3 -36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render 35641524,https://doi.org/10.1038/s41533-022-00280-0,Development and validation of a multivariable mortality risk prediction model for COPD in primary care.,"Shah SA, Nwaru BI, Sheikh A, Simpson CR, Kotz D.",,NPJ primary care respiratory medicine,2022,2022-05-31,Y,,,,"Risk stratification of chronic obstructive pulmonary disease (COPD) patients is important to enable targeted management. Existing disease severity classification systems, such as GOLD staging, do not take co-morbidities into account despite their high prevalence in COPD patients. We sought to develop and validate a prognostic model to predict 10-year mortality in patients with diagnosed COPD. We constructed a longitudinal cohort of 37,485 COPD patients (149,196 person-years) from a UK-wide primary care database. The risk factors included in the model pertained to demographic and behavioural characteristics, co-morbidities, and COPD severity. The outcome of interest was all-cause mortality. We fitted an extended Cox-regression model to estimate hazard ratios (HR) with 95% confidence intervals (CI), used machine learning-based data modelling approaches including k-fold cross-validation to validate the prognostic model, and assessed model fitting and discrimination. The inter-quartile ranges of the three metrics on the validation set suggested good performance: 0.90-1.06 for model fit, 0.80-0.83 for Harrel's c-index, and 0.40-0.46 for Royston and Saurebrei's [Formula: see text] with a strong overlap of these metrics on the training dataset. According to the validated prognostic model, the two most important risk factors of mortality were heart failure (HR 1.92; 95% CI 1.87-1.96) and current smoking (HR 1.68; 95% CI 1.66-1.71). We have developed and validated a national, population-based prognostic model to predict 10-year mortality of patients diagnosed with COPD. This model could be used to detect high-risk patients and modify risk factors such as optimising heart failure management and offering effective smoking cessation interventions.",,doi:https://doi.org/10.1038/s41533-022-00280-0; html:https://europepmc.org/articles/PMC9156666; pdf:https://europepmc.org/articles/PMC9156666?pdf=render +36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render 33837377,https://doi.org/10.1038/s41591-021-01310-z,Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.,"Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, Ho YL, Iyengar SK, Kosik NM, Vujkovic M, Gagnon DR, Bento AP, Barrio-Hernandez I, Rönnblom L, Hagberg N, Lundtoft C, Langenberg C, Pietzner M, Valentine D, Gustincich S, Tartaglia GG, Allara E, Surendran P, Burgess S, Zhao JH, Peters JE, Prins BP, Angelantonio ED, Devineni P, Shi Y, Lynch KE, DuVall SL, Garcon H, Thomann LO, Zhou JJ, Gorman BR, Huffman JE, O'Donnell CJ, Tsao PS, Beckham JC, Pyarajan S, Muralidhar S, Huang GD, Ramoni R, Beltrao P, Danesh J, Hung AM, Chang KM, Sun YV, Joseph J, Leach AR, Edwards TL, Cho K, Gaziano JM, Butterworth AS, Casas JP, VA Million Veteran Program COVID-19 Science Initiative.",,Nature medicine,2021,2021-04-09,Y,,,,"Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 × 10-6; IFNAR2, P = 9.8 × 10-11 and IL-10RB, P = 2.3 × 10-14) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.",,doi:https://doi.org/10.1038/s41591-021-01310-z; html:https://europepmc.org/articles/PMC7612986; pdf:https://europepmc.org/articles/PMC7612986?pdf=render; pdf:https://www.nature.com/articles/s41591-021-01310-z.pdf -37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,N,Depression; Mobile phone; Missing Data; Smartphones; Mobile Health; Wearable Devices; Behavioral Patterns; Digital Phenotypes,,,"

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,doi:https://doi.org/10.2196/45233; pdf:https://www.jmir.org/2023/1/e45233/PDF 32570434,https://doi.org/10.3233/shti200210,Using Unsupervised Learning to Identify Clinical Subtypes of Alzheimer's Disease in Electronic Health Records.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,Studies in health technology and informatics,2020,2020-06-01,N,Phenotyping; Alzheimer’s disease; Machine Learning; Electronic Health Records,,,"Identifying subtypes of Alzheimer's Disease (AD) can lead towards the creation of personalized interventions and potentially improve outcomes. In this study, we use UK primary care electronic health records (EHR) from the CALIBER resource to identify and characterize clinically-meaningful clusters patients using unsupervised learning approaches of MCA and K-means. We discovered and characterized five clusters with different profiles (mental health, non-typical AD, typical AD, CVD and men with cancer). The mental health cluster had faster rate of progression than all the other clusters making it a target for future research and intervention. Our results demonstrate that unsupervised learning approaches can be utilized on EHR to identify subtypes of heterogeneous conditions.",,doi:https://doi.org/10.3233/SHTI200210 35639667,https://doi.org/10.1093/eurheartj/ehac238,Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.,"van Smeden M, Heinze G, Van Calster B, Asselbergs FW, Vardas PE, Bruining N, de Jaegere P, Moore JH, Denaxas S, Boulesteix AL, Moons KGM.",,European heart journal,2022,2022-08-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health,,,"The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.",,doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render 36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"

Background

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

Methods

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

Results

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

Conclusions

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

Study registration number

NCT04330599.",,doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render; pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf @@ -1370,9 +1372,9 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35385889,https://doi.org/10.1515/dmpt-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,Genotyping; Stroke; aspirin; Clopidogrel; Cyp2c19*2,,,"

Objectives

To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Methods

This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay.

Results

From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele.

Conclusions

This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,doi:https://doi.org/10.1515/dmpt-2021-0104 34237806,https://doi.org/10.1515/dmdi-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. ,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,,,,"To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,doi:https://doi.org/10.1515/dmdi-2021-0104 33654696,https://doi.org/10.1093/burnst/tkaa044,Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients.,"Tracy LM, Cameron PA, Singer Y, Earnest A, Wood F, Cleland H, Gabbe BJ.",,Burns & trauma,2021,2021-01-01,Y,Australia; New Zealand; Burn injury; Prophylaxis; Venous Thromboembolism,,,"

Background

Patients with burn injuries are considered to have an increased risk of venous thromboembolism (VTE). While untreated VTEs can be fatal, no studies have examined chemoprophylaxis effectiveness. This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.

Methods

Admission data for adult burns patients (aged ≥16 years) admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand. Mixed effects logistic regression modelling investigated whether VTE prophylaxis use was associated with the primary outcome of in-hospital mortality.

Results

There were 5066 admissions over the study period. Of these patients, 81% (n = 3799) with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis. Use of VTE prophylaxis ranged from 48.6% to 94.8% of patients between units. In-hospital death was recorded in <1% of patients (n = 33). After adjusting for confounders, receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality (adjusted odds ratio = 0.21; 95% CI, 0.07-0.63; p = 0.006).

Conclusions

Variation in the use of VTE prophylaxis was observed between the units, and prophylaxis use was associated with a decrease in the odds of mortality. These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.",,doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render +35869125,https://doi.org/10.1038/s41598-022-16375-0,Minimising multi-centre radiomics variability through image normalisation: a pilot study.,"Campello VM, Martín-Isla C, Izquierdo C, Guala A, Palomares JFR, Viladés D, Descalzo ML, Karakas M, Çavuş E, Raisi-Estabragh Z, Petersen SE, Escalera S, Seguí S, Lekadir K.",,Scientific reports,2022,2022-07-22,Y,,,,"Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n = 112) and hypertrophic cardiomyopathy (n = 106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78 ± 0.08 and 0.79 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45 ± 0.28 and 0.60 ± 0.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.",,doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?pdf=render; pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf 37391266,https://doi.org/10.1016/s2589-7500(23)00087-0,Wearable technology and the cardiovascular system: the future of patient assessment.,"Williams GJ, Al-Baraikan A, Rademakers FE, Ciravegna F, van de Vosse FN, Lawrie A, Rothman A, Ashley EA, Wilkins MR, Lawford PV, Omholt SW, Wisløff U, Hose DR, Chico TJA, Gunn JP, Morris PD.",,The Lancet. Digital health,2023,2023-07-01,N,,,,"The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.",,doi:https://doi.org/10.1016/S2589-7500(23)00087-0 37096818,https://doi.org/10.1093/ehjacc/zuad042,"Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.","Gürgöze MT, Akkerhuis KM, Oemrawsingh RM, Umans VAWM, Kietselaer B, Schotborgh CE, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas AC, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans WRM, Cramer GE, van Gorp I, de Rijke YB, van Schaik RHN, Boersma E.",,European heart journal. Acute cardiovascular care,2023,2023-07-01,Y,Prognosis; Biomarkers; acute coronary syndrome; risk assessment; Repeated Measurements,,,"

Aims

Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.

Methods and results

BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).

Conclusion

Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.

Clinical trial registration

The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.",,doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render -35869125,https://doi.org/10.1038/s41598-022-16375-0,Minimising multi-centre radiomics variability through image normalisation: a pilot study.,"Campello VM, Martín-Isla C, Izquierdo C, Guala A, Palomares JFR, Viladés D, Descalzo ML, Karakas M, Çavuş E, Raisi-Estabragh Z, Petersen SE, Escalera S, Seguí S, Lekadir K.",,Scientific reports,2022,2022-07-22,Y,,,,"Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n = 112) and hypertrophic cardiomyopathy (n = 106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78 ± 0.08 and 0.79 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45 ± 0.28 and 0.60 ± 0.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.",,doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?pdf=render; pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf 32023934,https://doi.org/10.3390/ijerph17030892,Identifying Homogeneous Patterns of Injury in Paediatric Trauma Patients to Improve Risk-Adjusted Models of Mortality and Functional Outcomes. ,"Dipnall JF, Gabbe BJ, Teague WJ, Beck B.",,International journal of environmental research and public health,2020,2020-01-31,Y,,Improving Public Health,injuries and accidents,"Injury is a leading cause of morbidity and mortality in the paediatric population and exhibits complex injury patterns. This study aimed to identify homogeneous groups of paediatric major trauma patients based on their profile of injury for use in mortality and functional outcomes risk-adjusted models. Data were extracted from the population-based Victorian State Trauma Registry for patients aged 0-15 years, injured 2006-2016. Four Latent Class Analysis (LCA) models with/without covariates of age/sex tested up to six possible latent classes. Five risk-adjusted models of in-hospital mortality and 6-month functional outcomes incorporated a combination of Injury Severity Score (ISS), New ISS (NISS), and LCA classes. LCA models replicated the best log-likelihood and entropy > 0.8 for all models (N = 1281). Four latent injury classes were identified: isolated head; isolated abdominal organ; multi-trauma injuries, and other injuries. The best models, in terms of goodness of fit statistics and model diagnostics, included the LCA classes and NISS. The identification of isolated head, isolated abdominal, multi-trauma and other injuries as key latent paediatric injury classes highlights areas for emphasis in planning prevention initiatives and paediatric trauma system development. Future risk-adjusted paediatric injury models that include these injury classes with the NISS when evaluating mortality and functional outcomes is recommended.",,doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render 36560629,https://doi.org/10.3390/v14122625,Switching of Receptor Binding Poses between Closely Related Enteroviruses.,"Zhou D, Qin L, Duyvesteyn HME, Zhao Y, Lin TY, Fry EE, Ren J, Huang KA, Stuart DI.",,Viruses,2022,2022-11-24,Y,Evolution; Complex; Virus receptor; Glycan; Daf; Binding Pose; Echovirus E11; Enterovirus Structure,,,"Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier.",,doi:https://doi.org/10.3390/v14122625; html:https://europepmc.org/articles/PMC9781616; pdf:https://europepmc.org/articles/PMC9781616?pdf=render 37210036,https://doi.org/10.1016/j.jacc.2023.05.005,Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.,"Muller SA, Gasperetti A, Bosman LP, Schmidt AF, Baas AF, Amin AS, Houweling AC, Wilde AAM, Compagnucci P, Targetti M, Casella M, Calò L, Tondo C, van der Harst P, Asselbergs FW, van Tintelen JP, Oerlemans MIFJ, Te Riele ASJM.",,Journal of the American College of Cardiology,2023,2023-05-18,N,ventricular arrhythmia; Predictors; Screening Interval; Arvc; Family Screening,,,"

Background

Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives

The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Methods

A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with ""possible ARVC"" (only genetic or familial predisposition) and ""borderline ARVC"" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).

Results

At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05).

Conclusions

Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.",,doi:https://doi.org/10.1016/j.jacc.2023.05.005 @@ -1385,9 +1387,9 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34040552,https://doi.org/10.3389/fpsyt.2021.627996,Optimising a Simple Fully Convolutional Network for Accurate Brain Age Prediction in the PAC 2019 Challenge.,"Gong W, Beckmann CF, Vedaldi A, Smith SM, Peng H.",,Frontiers in psychiatry,2021,2021-05-10,Y,Brain imaging; Predictive Analysis; Big Data; Deep Learning; Convolution Neural Network; Brain Age Prediction,,,"Brain age prediction from brain MRI scans not only helps improve brain ageing modelling generally, but also provides benchmarks for predictive analysis methods. Brain-age delta, which is the difference between a subject's predicted age and true age, has become a meaningful biomarker for the health of the brain. Here, we report the details of our brain age prediction models and results in the Predictive Analysis Challenge 2019. The aim of the challenge was to use T1-weighted brain MRIs to predict a subject's age in multicentre datasets. We apply a lightweight deep convolutional neural network architecture, Simple Fully Convolutional Neural Network (SFCN), and combined several techniques including data augmentation, transfer learning, model ensemble, and bias correction for brain age prediction. The model achieved first place in both of the two objectives in the PAC 2019 brain age prediction challenge: Mean absolute error (MAE) = 2.90 years without bias removal (Second Place = 3.09 yrs; Third Place = 3.33 yrs), and MAE = 2.95 years with bias removal, leading by a large margin (Second Place = 3.80 yrs; Third Place = 3.92 yrs).",,doi:https://doi.org/10.3389/fpsyt.2021.627996; html:https://europepmc.org/articles/PMC8141616; pdf:https://europepmc.org/articles/PMC8141616?pdf=render 35047183,https://doi.org/10.7189/jogh.11.01011,The COVID-19 pandemic in children and young people during 2020-2021: A complex discussion on vaccination.,"Rudan I, Adeloye D, Katikireddi V, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01011; html:https://europepmc.org/articles/PMC8763337; pdf:https://europepmc.org/articles/PMC8763337?pdf=render 35047182,https://doi.org/10.7189/jogh.11.01010,"The COVID-19 pandemic in children and young people during 2020-2021: Learning about clinical presentation, patterns of spread, viral load, diagnosis and treatment.","Rudan I, Adeloye D, Katikireddi SV, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render +32393804,https://doi.org/10.1038/s41591-020-0916-2,Real-time tracking of self-reported symptoms to predict potential COVID-19.,"Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD.",,Nature medicine,2020,2020-05-11,N,,,,"A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.",,doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2; pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf 34930919,https://doi.org/10.1038/s41467-021-26280-1,Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome.,"Storm CS, Kia DA, Almramhi MM, Bandres-Ciga S, Finan C, International Parkinson’s Disease Genomics Consortium (IPDGC), Hingorani AD, Wood NW.",,Nature communications,2021,2021-12-20,Y,,,,"Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.",,doi:https://doi.org/10.1038/s41467-021-26280-1; html:https://europepmc.org/articles/PMC8688480; pdf:https://europepmc.org/articles/PMC8688480?pdf=render 35210596,https://doi.org/10.1038/s41591-022-01736-z,Modeling comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India.,"Du Z, Wang L, Pandey A, Lim WW, Chinazzi M, Piontti APY, Lau EHY, Wu P, Malani A, Cobey S, Cowling BJ.",,Nature medicine,2022,2022-02-24,Y,,,,"Given global Coronavirus Disease 2019 (COVID-19) vaccine shortages and inequity of vaccine distributions, fractionation of vaccine doses might be an effective strategy for reducing public health and economic burden, notwithstanding the emergence of new variants of concern. In this study, we developed a multi-scale model incorporating population-level transmission and individual-level vaccination to estimate the costs of hospitalization and vaccination and the economic benefits of reducing COVID-19 deaths due to dose-fractionation strategies in India. We used large-scale survey data of the willingness to pay together with data of vaccine and hospital admission costs to build the model. We found that fractional doses of vaccines could be an economically viable vaccination strategy compared to alternatives of either full-dose vaccination or no vaccination. Dose-sparing strategies could save a large number of lives, even with the emergence of new variants with higher transmissibility.",,doi:https://doi.org/10.1038/s41591-022-01736-z; html:https://europepmc.org/articles/PMC9117137; pdf:https://europepmc.org/articles/PMC9117137?pdf=render -32393804,https://doi.org/10.1038/s41591-020-0916-2,Real-time tracking of self-reported symptoms to predict potential COVID-19.,"Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD.",,Nature medicine,2020,2020-05-11,N,,,,"A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.",,doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2; pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf 32639589,https://doi.org/10.1111/bcp.14458,Measuring and reporting treatment adherence: What can we learn by comparing two respiratory conditions?,"Tibble H, Flook M, Sheikh A, Tsanas A, Horne R, Vrijens B, De Geest S, Stagg HR.",,British journal of clinical pharmacology,2021,2020-07-27,N,Tuberculosis; Adherence; Persistence; Asthma; Compliance,,,"Medication non-adherence, defined as any deviation from the regimen recommended by their healthcare provider, can increase morbidity, mortality and side effects, while reducing effectiveness. Through studying two respiratory conditions, asthma and tuberculosis (TB), we thoroughly review the current understanding of the measurement and reporting of medication adherence. In this paper, we identify major methodological issues in the standard ways that adherence has been conceptualised, defined and studied in asthma and TB. Between and within the two diseases there are substantial variations in adherence reporting, linked to differences in dosing intervals and treatment duration. Critically, the communicable nature of TB has resulted in dose-by-dose monitoring becoming a recommended treatment standard. Through the lens of these similarities and contrasts, we highlight contemporary shortcomings in the generalised conceptualisation of medication adherence. Furthermore, we outline elements in which knowledge could be directly transferred from one condition to the other, such as the application of large-scale cost-effective monitoring methods in TB to resource-poor settings in asthma. To develop a more robust evidence-based approach, we recommend the use of standard taxonomies detailed in the ABC taxonomy when measuring and discussing adherence. Regimen and intervention development and use should be based on sufficient evidence of the commonality and type of adherence behaviours displayed by patients with the relevant condition. A systematic approach to the measurement and reporting of adherence could improve the value and generalisability of research across all health conditions.",,doi:https://doi.org/10.1111/bcp.14458 36335192,https://doi.org/10.1038/s41598-022-22218-9,"Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.","Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.",,Scientific reports,2022,2022-11-05,Y,,,,"Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value < 5 × 10-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.",,doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render 34906385,https://doi.org/10.1016/j.burns.2021.07.025,Re: Re: Driving improved burns care and patient outcomes through clinical registry data: A review of quality indicators in the burns registry of Australia and New Zealand.,"Cleland H, Tracy LM, Singer Y, Wood F, Gong J, Cameron P, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2022,2021-08-12,N,,,,,,doi:https://doi.org/10.1016/j.burns.2021.07.025 @@ -1395,8 +1397,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34396190,https://doi.org/10.1016/j.jaccao.2019.09.007,Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics: What Is the Evidence?,"Kamphuis JAM, Linschoten M, Cramer MJ, Gort EH, van Rhenen A, Asselbergs FW, Doevendans PA, Teske AJ.",,JACC. CardioOncology,2019,2019-12-17,Y,"Cardiomyopathy; Heart Failure; Risk Prediction; Fda, Food And Drug Administration; Hf, Heart Failure; Mmc, Mitomycin C; Alkylating Therapy; Ctrcd, Cancer Therapy–Related Cardiac Dysfunction",,,"Cancer therapy-related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m2/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted.",,doi:https://doi.org/10.1016/j.jaccao.2019.09.007; html:https://europepmc.org/articles/PMC8352330; pdf:https://europepmc.org/articles/PMC8352330?pdf=render 32900377,https://doi.org/10.1186/s12916-020-01754-z,Going on up to the SPIRIT in AI: will new reporting guidelines for clinical trials of AI interventions improve their rigour?,"Wicks P, Liu X, Denniston AK.",,BMC medicine,2020,2020-09-09,Y,Artificial intelligence; Checklist; Clinical Trial; Machine Learning; Reporting Guidelines,,,,,doi:https://doi.org/10.1186/s12916-020-01754-z; html:https://europepmc.org/articles/PMC7487816; pdf:https://europepmc.org/articles/PMC7487816?pdf=render 32735547,https://doi.org/10.2196/20169,Can Robots Improve Testing Capacity for SARS-CoV-2?,"Cresswell K, Ramalingam S, Sheikh A.",,Journal of medical Internet research,2020,2020-08-12,Y,Virus; Infectious disease; Testing; Robotics; Pandemic; Covid-19; Sars-cov-2,,,"There is currently increasing interest internationally in deploying robotic applications for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as these can help to reduce the risk of transmission of the virus to health care staff and patients. We provide an overview of key recent developments in this area. We argue that, although there is some potential for deploying robots to help with SARS-CoV-2 testing, the potential of patient-facing applications is likely to be limited. This is due to the high costs associated with patient-facing functionality, and risks of potentially adverse impacts on health care staff work practices and patient interactions. In contrast, back-end laboratory-based robots dealing with sample extraction and amplification, that effectively integrate with established processes, software, and interfaces to process samples, are much more likely to result in safety and efficiency gains. Consideration should therefore be given to deploying these at scale.",,doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371 -33824163,https://doi.org/10.3399/bjgp20x714161,Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.,"Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-05-27,Y,Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network,,,"

Background

Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim

To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design and setting

Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method

Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results

A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion

This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.",,doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render; pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf 31965568,https://doi.org/10.1002/bjs.11433,Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.,"Singh P, Subramanian A, Adderley N, Gokhale K, Singhal R, Bellary S, Nirantharakumar K, Tahrani AA.",,The British journal of surgery,2020,2020-01-21,N,,,,"

Background

Cohort studies have shown that bariatric surgery may reduce the incidence of and mortality from cardiovascular disease (CVD), but studies using real-world data are limited. This study examined the impact of bariatric surgery on incident CVD, hypertension and atrial fibrillation, and all-cause mortality.

Methods

A retrospective, matched, controlled cohort study of The Health Improvement Network primary care database (from 1 January 1990 to 31 January 2018) was performed (approximately 6 per cent of the UK population). Adults with a BMI of 30 kg/m2 or above who did not have gastric cancer were included as the exposed group. Each exposed patient, who had undergone bariatric surgery, was matched for age, sex, BMI and presence of type 2 diabetes mellitus (T2DM) with two controls who had not had bariatric surgery.

Results

A total of 5170 exposed and 9995 control participants were included; their mean(s.d.) age was 45·3(10·5) years and 21·5 per cent (3265 of 15 165 participants) had T2DM. Median follow-up was 3·9 (i.q.r. 1·8- 6·4) years. Mean(s.d.) percentage weight loss was 20·0(13·2) and 0·8(9·5) per cent in exposed and control groups respectively. Overall, bariatric surgery was not associated with a significantly lower CVD risk (adjusted hazard ratio (HR) 0·80; 95 per cent c.i. 0·62 to 1·02; P = 0·074). Only in the gastric bypass group was a significant impact on CVD observed (HR 0·53, 0·34 to 0·81; P = 0·003). Bariatric surgery was associated with significant reduction in all-cause mortality (adjusted HR 0·70, 0·55 to 0·89; P = 0·004), hypertension (adjusted HR 0·41, 0·34 to 0·50; P < 0·001) and heart failure (adjusted HR 0·57, 0·34 to 0·96; P = 0·033). Outcomes were similar in patients with and those without T2DM (exposed versus controls), except for incident atrial fibrillation, which was reduced in the T2DM group.

Conclusion

Bariatric surgery is associated with a reduced risk of hypertension, heart failure and mortality, compared with routine care. Gastric bypass was associated with reduced risk of CVD compared to routine care.",,doi:https://doi.org/10.1002/bjs.11433 +33824163,https://doi.org/10.3399/bjgp20x714161,Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.,"Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-05-27,Y,Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network,,,"

Background

Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim

To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design and setting

Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method

Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results

A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion

This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.",,doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render; pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf 32200692,https://doi.org/10.1080/09602011.2020.1744453,Factors facilitating recovery following severe traumatic brain injury: A qualitative study.,"Downing M, Hicks A, Braaf S, Myles D, Gabbe B, Cameron P, Ameratunga S, Ponsford J.",,Neuropsychological rehabilitation,2021,2020-03-23,N,Recovery; Traumatic brain injury; Qualitative; Outcome; Positive Factors,,,"Given the significant impact of severe traumatic brain injury (TBI), understanding factors influencing recovery is critical to inform prognostication and treatment planning. Previous research has focussed primarily on factors negatively associated with outcome, with less focus on factors facilitating the recovery process. The current qualitative study examined positive factors identified for recovery by individuals who had sustained severe TBI three years earlier. Semi-structured interviews were conducted with nine participants with TBI and 16 close-others. Participants were asked to identify factors about themselves (or the injured individual), those around them, and the care they received that they felt were positive for recovery. Using reflexive thematic analysis, three themes were identified as positive for recovery after a TBI. Having a support network included social supports such as family and friends, and receiving other funded/non-funded assistance towards improving independence and participation. Being positive and engaged included being able to participate, being positive, using compensatory strategies, and becoming fit, healthy and happy. Getting good care included patients perceiving they had a comprehensive and good quality hospital experience, and access to multidisciplinary outpatient services. A focus on enhancing these positive environmental, personal and service factors in service provision may enhance outcomes following severe TBI.",,doi:https://doi.org/10.1080/09602011.2020.1744453 32907797,https://doi.org/10.1136/bmj.m3210,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI Extension.,"Rivera SC, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The SPIRIT 2013 (The Standard Protocol Items: Recommendations for Interventional Trials) statement aims to improve the completeness of clinical trial protocol reporting, by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there is a growing recognition that interventions involving artificial intelligence need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes.The SPIRIT-AI extension is a new reporting guideline for clinical trials protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI. Both guidelines were developed using a staged consensus process, involving a literature review and expert consultation to generate 26 candidate items, which were consulted on by an international multi-stakeholder group in a 2-stage Delphi survey (103 stakeholders), agreed on in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The SPIRIT-AI extension includes 15 new items, which were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations around the handling of input and output data, the human-AI interaction and analysis of error cases.SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.",,doi:https://doi.org/10.1136/bmj.m3210; html:https://europepmc.org/articles/PMC7490785 31816119,https://doi.org/10.1002/sim.8443,Dynamic predictive probabilities to monitor rapid cystic fibrosis disease progression.,"Szczesniak RD, Su W, Brokamp C, Keogh RH, Pestian JP, Seid M, Diggle PJ, Clancy JP.",,Statistics in medicine,2020,2019-12-09,Y,Longitudinal Data Analysis; Medical Monitoring; Nonstationary Process; Nowcasting; Predictive Probability Distributions,Understanding the Causes of Disease,,"Cystic fibrosis (CF) is a progressive, genetic disease characterized by frequent, prolonged drops in lung function. Accurately predicting rapid underlying lung-function decline is essential for clinical decision support and timely intervention. Determining whether an individual is experiencing a period of rapid decline is complicated due to its heterogeneous timing and extent, and error component of the measured lung function. We construct individualized predictive probabilities for ""nowcasting"" rapid decline. We assume each patient's true longitudinal lung function, S(t), follows a nonlinear, nonstationary stochastic process, and accommodate between-patient heterogeneity through random effects. Corresponding lung-function decline at time t is defined as the rate of change, S'(t). We predict S'(t) conditional on observed covariate and measurement history by modeling a measured lung function as a noisy version of S(t). The method is applied to data on 30 879 US CF Registry patients. Results are contrasted with a currently employed decision rule using single-center data on 212 individuals. Rapid decline is identified earlier using predictive probabilities than the center's currently employed decision rule (mean difference: 0.65 years; 95% confidence interval (CI): 0.41, 0.89). We constructed a bootstrapping algorithm to obtain CIs for predictive probabilities. We illustrate real-time implementation with R Shiny. Predictive accuracy is investigated using empirical simulations, which suggest this approach more accurately detects peak decline, compared with a uniform threshold of rapid decline. Median area under the ROC curve estimates (Q1-Q3) were 0.817 (0.814-0.822) and 0.745 (0.741-0.747), respectively, implying reasonable accuracy for both. This article demonstrates how individualized rate of change estimates can be coupled with probabilistic predictive inference and implementation for a useful medical-monitoring approach.",The objective of this paper was to construct individualised dynamic predictive probabilities to monitor rapid Cystic Fibrosis (CF) disease progression. The results demonstrated how individualised rate of change estimates can be coupled with probabilitic predictive inference and implementation for a useful medical-monitoring approach.,doi:https://doi.org/10.1002/sim.8443; html:https://europepmc.org/articles/PMC7028099; pdf:https://europepmc.org/articles/PMC7028099?pdf=render @@ -1422,8 +1424,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 36962407,https://doi.org/10.1371/journal.pgph.0000292,Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.,"van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",,PLOS global public health,2022,2022-07-07,Y,,,,"Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",,doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render 32079223,https://doi.org/10.3390/jcm9020545,Quantitative Approach to Fragmented QRS in Arrhythmogenic Cardiomyopathy: From Disease towards Asymptomatic Carriers of Pathogenic Variants. ,"Roudijk RW, Bosman LP, van der Heijden JF, de Bakker JMT, Hauer RNW, van Tintelen JP, Asselbergs FW, Te Riele ASJM, Loh P.",,Journal of clinical medicine,2020,2020-02-17,Y,,Understanding the Causes of Disease,cardiovascular,"Fragmented QRS complexes (fQRS) are common in patients with arrhythmogenic cardiomyopathy (ACM). A new method of fQRS quantification may aid early disease detection in pathogenic variant carriers and assessment of prognosis in patients with early stage ACM. Patients with definite ACM (n = 221, 66%), carriers of a pathogenic ACM-associated variant without a definite ACM diagnosis (n = 57, 17%) and control subjects (n = 58, 17%) were included. Quantitative fQRS (Q-fQRS) was defined as the total amount of deflections in the QRS complex in all 12 electrocardiography (ECG) leads. Q-fQRS was scored by a single observer and reproducibility was determined by three independent observers. Q-fQRS count was feasible with acceptable intra- and inter-observer agreement. Q-fQRS count is significantly higher in patients with definite ACM (54 ± 15) and pathogenic variant carriers (55 ± 10) compared to controls (35 ± 5) (p < 0.001). In patients with ACM, Q-fQRS was not associated with sustained ventricular arrhythmia (p = 0.701) at baseline or during follow-up (p = 0.335). Both definite ACM patients and pathogenic variant carriers not fulfilling ACM diagnosis have a higher Q-fQRS than controls. This may indicate that increased Q-fQRS is an early sign of disease penetrance. In concealed and early stages of ACM the role of Q-fQRS for risk stratification is limited.",,doi:https://doi.org/10.3390/jcm9020545; html:https://europepmc.org/articles/PMC7073517; pdf:https://europepmc.org/articles/PMC7073517?pdf=render 35165324,https://doi.org/10.1038/s41598-022-06315-3,Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.,"Gheorghiță BA, Itu LM, Sharma P, Suciu C, Wetzl J, Geppert C, Ali MAA, Lee AM, Piechnik SK, Neubauer S, Petersen SE, Schulz-Menger J, Chițiboi T.",,Scientific reports,2022,2022-02-14,Y,,,,"Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.",,doi:https://doi.org/10.1038/s41598-022-06315-3; html:https://europepmc.org/articles/PMC8844403; pdf:https://europepmc.org/articles/PMC8844403?pdf=render -35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Aefi, Adverse Events Following Immunisation; Mic, Middle Income Country",,,"

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render 30848519,https://doi.org/10.1111/dme.13945,Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis.,"Thayakaran R, Perrins M, Gokhale KM, Kumaran S, Narendran P, Price MJ, Nirantharakumar K, Toulis KA.",,Diabetic medicine : a journal of the British Diabetic Association,2019,2019-04-05,N,,,,"

Aims

To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes.

Methods

People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA1c included as a time-dependent variable was fitted to these data.

Results

Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002-1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03-1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c .

Conclusions

In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures.",,doi:https://doi.org/10.1111/dme.13945 +35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Aefi, Adverse Events Following Immunisation; Mic, Middle Income Country",,,"

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render 35241573,https://doi.org/10.1136/bmjqs-2020-012108,Comparing antibiotic prescribing between clinicians in UK primary care: an analysis in a cohort study of eight different measures of antibiotic prescribing.,"Van Staa T, Li Y, Gold N, Chadborn T, Welfare W, Palin V, Ashcroft DM, Bircher J.",,BMJ quality & safety,2022,2022-03-03,Y,General Practice; Antibiotic Management; Healthcare Quality Improvement,,,"

Background

There is a need to reduce antimicrobial uses in humans. Previous studies have found variations in antibiotic (AB) prescribing between practices in primary care. This study assessed variability of AB prescribing between clinicians.

Methods

Clinical Practice Research Datalink, which collects electronic health records in primary care, was used to select anonymised clinicians providing 500+ consultations during 2012-2017. Eight measures of AB prescribing were assessed, such as overall and incidental AB prescribing, repeat AB courses and extent of risk-based prescribing. Poisson regression models with random effect for clinicians were fitted.

Results

6111 clinicians from 466 general practices were included. Considerable variability between individual clinicians was found for most AB measures. For example, the rate of AB prescribing varied between 77.4 and 350.3 per 1000 consultations; percentage of repeat AB courses within 30 days ranged from 13.1% to 34.3%; predicted patient risk of hospital admission for infection-related complications in those prescribed AB ranged from 0.03% to 0.32% (5th and 95th percentiles). The adjusted relative rate between clinicians in rates of AB prescribing was 5.23. Weak correlation coefficients (<0.5) were found between most AB measures. There was considerable variability in case mix seen by clinicians. The largest potential impact to reduce AB prescribing could be around encouraging risk-based prescribing and addressing repeat issues of ABs. Reduction of repeat AB courses to prescribing habit of median clinician would save 21 813 AB prescriptions per 1000 clinicians per year.

Conclusions

The wide variation seen in all measures of AB prescribing and weak correlation between them suggests that a single AB measure, such as prescribing rate, is not sufficient to underpin the optimisation of AB prescribing.",,doi:https://doi.org/10.1136/bmjqs-2020-012108; html:https://europepmc.org/articles/PMC9606525; pdf:https://europepmc.org/articles/PMC9606525?pdf=render 36936592,https://doi.org/10.1136/bmjmed-2022-000151,Covid-19 variants of concern and pregnancy.,"Stock SJ, Harmer C, Calvert C.",,BMJ medicine,2022,2022-03-02,Y,Pregnancy complications; Covid-19,,,,,doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render 34859219,https://doi.org/10.1093/braincomms/fcab275,Maternal immune activation downregulates schizophrenia genes in the foetal mouse brain.,"Handunnetthi L, Saatci D, Hamley JC, Knight JC.",,Brain communications,2021,2021-11-15,Y,Infection; Genetics; Schizophrenia; Immune; Maternal,,,"Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10-4) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10-10). We found that these genes mapped to key biological processes, such as neuronal cell adhesion. We also identified cortical excitatory neurons and inhibitory interneurons as the most vulnerable cell types to the deleterious effects of this interaction. Subsequently, we used gene expression information from herpes simplex virus 1 infection of neuronal precursor cells as orthogonal evidence to support our findings and to demonstrate that schizophrenia-associated cell adhesion genes, PCDHA2, PCDHA3 and PCDHA5, were downregulated following herpes simplex virus 1 infection. Collectively, our results provide novel evidence for a link between genetic and environmental risk factors in schizophrenia pathogenesis. These findings carry important implications for early preventative strategies in schizophrenia.",,doi:https://doi.org/10.1093/braincomms/fcab275; html:https://europepmc.org/articles/PMC8633770; pdf:https://europepmc.org/articles/PMC8633770?pdf=render @@ -1434,8 +1436,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35212847,https://doi.org/10.1007/s00455-022-10425-5,Identifying Dysphagia and Demographic Associations in Older Adults Using Electronic Health Records: A National Longitudinal Observational Study in Wales (United Kingdom) 2008-2018.,"Hollinghurst J, Smithard DG.",,Dysphagia,2022,2022-02-25,Y,Prevalence; Frailty; epidemiology; Old Age; Dysphagia; Deprivation,,,"Dysphagia is increasingly being recognised as a geriatric syndrome (giant). There is limited research on the prevalence of dysphagia using electronic health records. To investigate associations between dysphagia, as recorded in electronic health records and age, frailty using the electronic frailty index, gender and deprivation (Welsh index of multiple deprivation). A Cross-sectional longitudinal cohort study in over 400,000 older adults was undertaken (65 +) in Wales (United Kingdom) per year from 2008 to 2018. We used the secure anonymised information linkage databank to identify dysphagia diagnoses in primary and secondary care. We used chi-squared tests and multivariate logistic regression to investigate associations between dysphagia diagnosis and age, frailty (using the electronic Frailty index), gender and deprivation. Data indicated < 1% of individuals were recorded as having a dysphagia diagnosis per year. We found dysphagia to be statistically significantly associated with older age, more severe frailty and individuals from more deprived areas. Multivariate analyses indicated increased odds ratios [OR (95% confidence intervals)] for a dysphagia diagnosis with increased age [reference 65-74: aged 75-84 OR 1.09 (1.07, 1.12), 85 + OR 1.23 (1.20, 1.27)], frailty (reference fit: mild frailty 2.45 (2.38, 2.53), moderate frailty 4.64 (4.49, 4.79) and severe frailty 7.87 (7.55, 8.21)] and individuals from most deprived areas [reference 5. Least deprived, 1. Most deprived: 1.10 (1.06, 1.14)]. The study has identified that prevalence of diagnosed dysphagia is lower than previously reported. This study has confirmed the association of dysphagia with increasing age and frailty. A previously unreported association with deprivation has been identified. Deprivation is a multifactorial problem that is known to affect health outcomes, and the association with dysphagia should not be a surprise. Research in to this relationship is indicated.",,doi:https://doi.org/10.1007/s00455-022-10425-5; html:https://europepmc.org/articles/PMC9643178; pdf:https://europepmc.org/articles/PMC9643178?pdf=render 34112101,https://doi.org/10.1186/s12872-021-02020-7,Routine clinical care data from thirteen cardiac outpatient clinics: design of the Cardiology Centers of the Netherlands (CCN) database.,"Bots SH, Siegersma KR, Onland-Moret NC, Asselbergs FW, Somsen GA, Tulevski II, den Ruijter HM, Hofstra L.",,BMC cardiovascular disorders,2021,2021-06-10,Y,Prevention; Big Data; Cardiovascular Care; Clinical Care Data,,,"

Background

Despite the increasing availability of clinical data due to the digitalisation of healthcare systems, data often remain inaccessible due to the diversity of data collection systems. In the Netherlands, Cardiology Centers of the Netherlands (CCN) introduced ""one-stop shop"" diagnostic clinics for patients suspected of cardiac disease by their general practitioner. All CCN clinics use the same data collection system and standardised protocol, creating a large regular care database. This database can be used to describe referral practices, evaluate risk factors for cardiovascular disease (CVD) in important patient subgroups, and develop prediction models for use in daily care.

Construction and content

The current database contains data on all patients who underwent a cardiac workup in one of the 13 CCN clinics between 2007 and February 2018 (n = 109,151, 51.9% women). Data were pseudonymised and contain information on anthropometrics, cardiac symptoms, risk factors, comorbidities, cardiovascular and family history, standard blood laboratory measurements, transthoracic echocardiography, electrocardiography in rest and during exercise, and medication use. Clinical follow-up is based on medical need and consisted of either a repeat visit at CCN (43.8%) or referral for an external procedure in a hospital (16.5%). Passive follow-up via linkage to national mortality registers is available for 95% of the database.

Utility and discussion

The CCN database provides a strong base for research into historically underrepresented patient groups due to the large number of patients and the lack of in- and exclusion criteria. It also enables the development of artificial intelligence-based decision support tools. Its contemporary nature allows for comparison of daily care with the current guidelines and protocols. Missing data is an inherent limitation, as the cardiologist could deviate from standardised protocols when clinically indicated.

Conclusion

The CCN database offers the opportunity to conduct research in a unique population referred from the general practitioner to the cardiologist for diagnostic workup. This, in combination with its large size, the representation of historically underrepresented patient groups and contemporary nature makes it a valuable tool for expanding our knowledge of cardiovascular diseases.

Trial registration

Not applicable.",,doi:https://doi.org/10.1186/s12872-021-02020-7; html:https://europepmc.org/articles/PMC8191101; pdf:https://europepmc.org/articles/PMC8191101?pdf=render 32573463,https://doi.org/10.2196/18185,Superusers' Engagement in Asthma Online Communities: Asynchronous Web-Based Interview Study.,"De Simoni A, Shah AT, Fulton O, Parkinson J, Sheikh A, Panzarasa P, Pagliari C, Coulson NS, Griffiths CJ.",,Journal of medical Internet research,2020,2020-06-23,Y,Asthma; Misinformation; Social Networks; Leadership; Social Support; Self-management; Social Media; Ehealth; Online Health Communities; Superusers; Online Forums; Peer-to-peer Support,,,"

Background

Superusers, defined as the 1% of users who write a large number of posts, play critical roles in online health communities (OHCs), catalyzing engagement and influencing other users' self-care. Their unique online behavior is key to sustaining activity in OHCs and making them flourish. Our previous work showed the presence of 20 to 30 superusers active on a weekly basis among 3345 users in the nationwide Asthma UK OHC and that the community would disintegrate if superusers were removed. Recruiting these highly skilled individuals for research purposes can be challenging, and little is known about superusers.

Objective

This study aimed to explore superusers' motivation to actively engage in OHCs, the difficulties they may face, and their interactions with health care professionals (HCPs).

Methods

An asynchronous web-based structured interview study was conducted. Superusers of the Asthma UK OHC and Facebook groups were recruited through Asthma UK staff to pilot and subsequently complete the questionnaire. Open-ended questions were analyzed using content analysis.

Results

There were 17 superusers recruited for the study (14 patients with asthma and 3 carers); the majority were female (15/17). The age range of participants was 18 to 75 years. They were active in OHCs for 1 to 6 years and spent between 1 and 20 hours per week reading and 1 and 3 hours per week writing posts. Superusers' participation in OHCs was prompted by curiosity about asthma and its medical treatment and by the availability of spare time when they were off work due to asthma exacerbations or retired. Their engagement increased over time as participants furthered their familiarity with the OHCs and their knowledge of asthma and its self-management. Financial or social recognition of the superuser role was not important; their reward came from helping and interacting with others. According to the replies provided, they showed careful judgment to distinguish what can be dealt with through peer advice and what needs input from HCPs. Difficulties were encountered when dealing with misunderstandings about asthma and its treatment, patients not seeking advice from HCPs when needed, and miracle cures or dangerous ideas. Out of 17 participants, only 3 stated that their HCPs were aware of their engagement with OHCs. All superusers thought that HCPs should direct patients to OHCs, provided they are trusted and moderated. In addition, 9 users felt that HCPs themselves should take part in OHCs.

Conclusions

Superusers from a UK-wide online community are highly motivated, altruistic, and mostly female individuals who exhibit judgment about the complexity of coping with asthma and the limits of their advice. Engagement with OHCs satisfies their psychosocial needs. Future research should explore how to address their unmet needs, their interactions with HCPs, and the potential integration of OHCs in traditional healthcare.",,doi:https://doi.org/10.2196/18185; html:https://europepmc.org/articles/PMC7381072 -33306713,https://doi.org/10.1371/journal.pone.0243383,"Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.","Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,PloS one,2020,2020-12-11,Y,,,,"

Background

To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.

Methods

This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.

Results

After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.

Conclusions

Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.",,doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render 33310109,https://doi.org/10.1016/j.ijid.2020.12.006,"Response to ""Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients"".","Linschoten M, Nab L, van der Horst ICC, Tieleman R, Asselbergs FW.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2021,2020-12-09,Y,,,,,,doi:https://doi.org/10.1016/j.ijid.2020.12.006; html:https://europepmc.org/articles/PMC7725132; pdf:https://europepmc.org/articles/PMC7725132?pdf=render +33306713,https://doi.org/10.1371/journal.pone.0243383,"Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.","Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,PloS one,2020,2020-12-11,Y,,,,"

Background

To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.

Methods

This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.

Results

After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.

Conclusions

Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.",,doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render 32679111,https://doi.org/10.1016/s0140-6736(20)31356-8,COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.,"Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, Hollings S, Roebuck C, Gale CP, Mamas MA, Deanfield JE, de Belder MA, Luescher TF, Denwood T, Landray MJ, Emberson JR, Collins R, Morris EJA, Casadei B, Baigent C.",,"Lancet (London, England)",2020,2020-07-14,Y,,,,"

Background

Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.

Methods

We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.

Findings

Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.

Interpretation

Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.

Funding

UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.",,doi:https://doi.org/10.1016/S0140-6736(20)31356-8; html:https://europepmc.org/articles/PMC7429983; pdf:https://europepmc.org/articles/PMC7429983?pdf=render 32371477,https://doi.org/10.1126/science.abc0473,Rapid implementation of mobile technology for real-time epidemiology of COVID-19.,"Drew DA, Nguyen LH, Steves CJ, Menni C, Freydin M, Varsavsky T, Sudre CH, Cardoso MJ, Ourselin S, Wolf J, Spector TD, Chan AT, COPE Consortium.",,"Science (New York, N.Y.)",2020,2020-05-05,Y,,,,"The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application-which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots-was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge.","Drew et al. decribe the use of a smart-phone App to track Covid-19 symptoms reported by users to track, in real time, information on newly infected individuals. It has been launched in the UK and US and has 2.8 million users and is used to rapidly identify emerging hot spots for infection.",doi:https://doi.org/10.1126/science.abc0473; html:https://europepmc.org/articles/PMC7200009; pdf:https://europepmc.org/articles/PMC7200009?pdf=render 33048945,https://doi.org/10.1371/journal.pmed.1003290,Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.,"Fleming M, Salim EE, Mackay DF, Henderson A, Kinnear D, Clark D, King A, McLay JS, Cooper SA, Pell JP.",,PLoS medicine,2020,2020-10-13,Y,,,,"

Background

Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.

Conclusions

Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.",,doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?pdf=render @@ -1451,8 +1453,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35861818,https://doi.org/10.1161/jaha.121.025473,Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.,"Henkens MTHM, López Martínez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bayés-de-Luna A, Asselbergs FW, Bayés-Genís A, Heymans SRB.",,Journal of the American Heart Association,2022,2022-07-15,Y,Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non‐ischemic Cardiomyopathy; Life‐threatening Arrhythmias,,,"Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120 milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4 years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.",,doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render 36048760,https://doi.org/10.1371/journal.pgen.1010294,Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer's disease.,"Paranjpe MD, Chaffin M, Zahid S, Ritchie S, Rotter JI, Rich SS, Gerszten R, Guo X, Heckbert S, Tracy R, Danesh J, Lander ES, Inouye M, Kathiresan S, Butterworth AS, Khera AV.",,PLoS genetics,2022,2022-09-01,Y,,,,"For Alzheimer's disease-a leading cause of dementia and global morbidity-improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer's disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer's disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p < 0.001) gradient in risk across deciles of the score among 288,289 middle-aged participants of the UK Biobank study. In cross-sectional analyses stratified by age, minimal differences in risk of Alzheimer's disease and performance on a digit recall test were present according to polygenic score decile at age 50 years, but significant gradients emerged by age 65. Similarly, among 30,541 participants of the Mass General Brigham Biobank, we again noted no significant differences in Alzheimer's disease diagnosis at younger ages across deciles of the score, but for those over 65 years we noted an odds ratio of 2.0 (95% CI 1.3 to 3.2; p = 0.002) in the top versus bottom decile of the polygenic score. To understand the proteomic signature of inherited risk, we performed aptamer-based profiling in 636 blood donors (mean age 43 years) with very high or low polygenic scores. In addition to the well-known apolipoprotein E biomarker, this analysis identified 27 additional proteins, several of which have known roles related to disease pathogenesis. Differences in protein concentrations were consistent even among the youngest subset of blood donors (mean age 33 years). Of these 28 proteins, 7 of the 8 proteins with concentrations available were similarly associated with the polygenic score in participants of the Multi-Ethnic Study of Atherosclerosis. These data highlight the potential for a DNA-based score to identify high-risk individuals during the prolonged presymptomatic phase of Alzheimer's disease and to enable biomarker discovery based on profiling of young individuals in the extremes of the score distribution.",,doi:https://doi.org/10.1371/journal.pgen.1010294; html:https://europepmc.org/articles/PMC9436054; pdf:https://europepmc.org/articles/PMC9436054?pdf=render 30444743,https://doi.org/10.1097/ccm.0000000000003424,"Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.","Szakmany T, Walters AM, Pugh R, Battle C, Berridge DM, Lyons RA.",,Critical care medicine,2019,2019-01-01,N,,,,"

Objectives

Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group.

Design

Population-based data linkage study using the Secure Anonymised Information Linkage databank.

Setting

All ICUs between 2006 and 2013 in Wales, United Kingdom.

Patients

We identified 40,631 patients discharged alive from Welsh adult ICUs.

Interventions

None.

Measurements and main results

Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively.

Conclusions

One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.",,doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424 -37060915,https://doi.org/10.1016/s0140-6736(23)00510-x,"Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.",,"Lancet (London, England)",2023,2023-04-13,Y,,,,"

Background

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

Methods

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

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render 34226637,https://doi.org/10.1038/s41366-021-00896-1,Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates.,"Goudswaard LJ, Bell JA, Hughes DA, Corbin LJ, Walter K, Davey Smith G, Soranzo N, Danesh J, Di Angelantonio E, Ouwehand WH, Watkins NA, Roberts DJ, Butterworth AS, Hers I, Timpson NJ.",,International journal of obesity (2005),2021,2021-07-05,Y,,,,"

Background

Variation in adiposity is associated with cardiometabolic disease outcomes, but mechanisms leading from this exposure to disease are unclear. This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins.

Methods

We used SomaLogic proteomic data from up to 2737 healthy participants from the INTERVAL study. Associations between self-reported BMI and 3622 unique plasma proteins were explored using linear regression. These were complemented by Mendelian randomisation (MR) analyses using a genetic risk score (GRS) comprised of 654 BMI-associated polymorphisms from a recent genome-wide association study (GWAS) of adult BMI. A disease enrichment analysis was performed using DAVID Bioinformatics 6.8 for proteins which were altered by BMI.

Results

Observationally, BMI was associated with 1576 proteins (P < 1.4 × 10-5), with particularly strong evidence for a positive association with leptin and fatty acid-binding protein-4 (FABP4), and a negative association with sex hormone-binding globulin (SHBG). Observational estimates were likely confounded, but the GRS for BMI did not associate with measured confounders. MR analyses provided evidence for a causal relationship between BMI and eight proteins including leptin (0.63 standard deviation (SD) per SD BMI, 95% CI 0.48-0.79, P = 1.6 × 10-15), FABP4 (0.64 SD per SD BMI, 95% CI 0.46-0.83, P = 6.7 × 10-12) and SHBG (-0.45 SD per SD BMI, 95% CI -0.65 to -0.25, P = 1.4 × 10-5). There was agreement in the magnitude of observational and MR estimates (R2 = 0.33) and evidence that proteins most strongly altered by BMI were enriched for genes involved in cardiovascular disease.

Conclusions

This study provides evidence for a broad impact of adiposity on the human proteome. Proteins strongly altered by BMI include those involved in regulating appetite, sex hormones and inflammation; such proteins are also enriched for cardiovascular disease-related genes. Altogether, results help focus attention onto new proteomic signatures of obesity-related disease.",,doi:https://doi.org/10.1038/s41366-021-00896-1; html:https://europepmc.org/articles/PMC8455324; pdf:https://europepmc.org/articles/PMC8455324?pdf=render +37060915,https://doi.org/10.1016/s0140-6736(23)00510-x,"Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.",,"Lancet (London, England)",2023,2023-04-13,Y,,,,"

Background

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

Methods

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

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render 32909959,https://doi.org/10.1136/bmj.m3164,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI Extension.,"Liu X, Rivera SC, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The CONSORT 2010 (Consolidated Standards of Reporting Trials) statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency when evaluating new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes.The CONSORT-AI extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI. Both guidelines were developed through a staged consensus process, involving a literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed on in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The CONSORT-AI extension includes 14 new items, which were considered sufficiently important for AI interventions, that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and providing analysis of error cases.CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,doi:https://doi.org/10.1136/bmj.m3164; html:https://europepmc.org/articles/PMC7490784 35045937,https://doi.org/10.1016/j.amjcard.2021.12.022,Relation of Iron Status to Prognosis After Acute Coronary Syndrome.,"Gürgöze MT, Kardys I, Akkerhuis KM, Oemrawsingh RM, Groot HE, van der Harst P, Umans VA, Kietselaer B, Ronner E, Lenderink T, Asselbergs FW, Manintveld OC, Boersma E.",,The American journal of cardiology,2022,2022-01-16,N,,,,"Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.",,doi:https://doi.org/10.1016/j.amjcard.2021.12.022 35193912,https://doi.org/10.1136/bmjopen-2021-053884,"Variation in health visiting contacts for children in England: cross-sectional analysis of the 2-2½ year review using administrative data (Community Services Dataset, CSDS).","Fraser C, Harron K, Barlow J, Bennett S, Woods G, Shand J, Kendall S, Woodman J.",,BMJ open,2022,2022-02-22,Y,Public Health; Community Child Health; Child Protection; Organisation Of Health Services,,,"

Objective

The 2-2½ year universal health visiting review in England is a key time point for assessing child development and promoting school readiness. We aimed to ascertain which children were least likely to receive their 2-2½ year review and whether there were additional non-mandated contacts for children who missed this review.

Design, setting, participants

Cross-sectional analysis of the 2-2½ year review and additional health visiting contacts for 181 130 children aged 2 in England 2018/2019, stratified by ethnicity, deprivation, safeguarding vulnerability indicator and Looked After Child status.

Analysis

We used data from 33 local authorities submitting highly complete data on health visiting contacts to the Community Services Dataset. We calculated the percentage of children with a recorded 2-2½ year review and/or any additional health visiting contacts and average number of contacts, by child characteristic.

Results

The most deprived children were slightly less likely to receive a 2-2½ year review than the least deprived children (72% vs 78%) and Looked After Children much less likely, compared with other children (44% vs 69%). When all additional contacts were included, the pattern was reversed (deprivation) or disappeared (Looked After children). A substantial proportion of all children (24%), children with a 'safeguarding vulnerability' (22%) and Looked After children (29%) did not have a record of either a 2-2½ year review or any other face-to-face contact in the year.

Conclusions

A substantial minority of children aged 2 with known vulnerabilities did not see the health visiting team at all in the year. Some higher need children (eg, deprived and Looked After) appeared to be seeing the health visiting team but not receiving their mandated health review. Further work is needed to establish the reasons for this, and potential solutions. There is an urgent need to improve the quality of national health visiting data.",,doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render @@ -1465,10 +1467,10 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34328441,https://doi.org/10.2196/29840,Predicting Depressive Symptom Severity Through Individuals' Nearby Bluetooth Device Count Data Collected by Mobile Phones: Preliminary Longitudinal Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Matcham F, Oetzmann C, Lamers F, Siddi S, Simblett S, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Annas P, Hotopf M, Dobson RJB.",,JMIR mHealth and uHealth,2021,2021-07-30,Y,Monitoring; Depression; Mental health; Hierarchical Bayesian Model; Bluetooth; Mhealth; Mobile Health; Digital Health; Digital Biomarkers; Digital Phenotyping,,,"

Background

Research in mental health has found associations between depression and individuals' behaviors and statuses, such as social connections and interactions, working status, mobility, and social isolation and loneliness. These behaviors and statuses can be approximated by the nearby Bluetooth device count (NBDC) detected by Bluetooth sensors in mobile phones.

Objective

This study aimed to explore the value of the NBDC data in predicting depressive symptom severity as measured via the 8-item Patient Health Questionnaire (PHQ-8).

Methods

The data used in this paper included 2886 biweekly PHQ-8 records collected from 316 participants recruited from three study sites in the Netherlands, Spain, and the United Kingdom as part of the EU Remote Assessment of Disease and Relapse-Central Nervous System (RADAR-CNS) study. From the NBDC data 2 weeks prior to each PHQ-8 score, we extracted 49 Bluetooth features, including statistical features and nonlinear features for measuring the periodicity and regularity of individuals' life rhythms. Linear mixed-effect models were used to explore associations between Bluetooth features and the PHQ-8 score. We then applied hierarchical Bayesian linear regression models to predict the PHQ-8 score from the extracted Bluetooth features.

Results

A number of significant associations were found between Bluetooth features and depressive symptom severity. Generally speaking, along with depressive symptom worsening, one or more of the following changes were found in the preceding 2 weeks of the NBDC data: (1) the amount decreased, (2) the variance decreased, (3) the periodicity (especially the circadian rhythm) decreased, and (4) the NBDC sequence became more irregular. Compared with commonly used machine learning models, the proposed hierarchical Bayesian linear regression model achieved the best prediction metrics (R2=0.526) and a root mean squared error (RMSE) of 3.891. Bluetooth features can explain an extra 18.8% of the variance in the PHQ-8 score relative to the baseline model without Bluetooth features (R2=0.338, RMSE=4.547).

Conclusions

Our statistical results indicate that the NBDC data have the potential to reflect changes in individuals' behaviors and statuses concurrent with the changes in the depressive state. The prediction results demonstrate that the NBDC data have a significant value in predicting depressive symptom severity. These findings may have utility for the mental health monitoring practice in real-world settings.",,doi:https://doi.org/10.2196/29840; html:https://europepmc.org/articles/PMC8367113 35880304,https://doi.org/10.1002/jbmr.4664,Telomere Length and Risk of Incident Fracture and Arthroplasty: Findings From UK Biobank.,"Curtis EM, Codd V, Nelson C, D'Angelo S, Wang Q, Allara E, Kaptoge S, Matthews PM, Tobias JH, Danesh J, Cooper C, Samani NJ, Harvey NC.",,Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,2022,2022-09-13,Y,Aging; Osteoporosis; Osteoarthritis; epidemiology; Leucocyte Telomere Length,,,"We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leukocyte telomere length (LTL) was measured in baseline samples using a validated polymerase chain reaction (PCR) method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio (HR) for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person-years of follow-up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity, and menopause (women). In further analyses we adjusted for either estimated bone mineral density (eBMD) from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance), or blood biomarkers, all measured at baseline (2006-2010). We studied 59,500 women and 51,895 men, mean ± standard deviation (SD) age 56.4 ± 8.0 and 57.0 ± 8.3 years, respectively. During follow-up there were 5619 fractures; 5285 hip and 4261 knee arthroplasties. In confounder-adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men (HR/SD 0.93; 95% confidence interval [CI], 0.88-0.97) and women (0.92; 95% CI, 0.88-0.96), and hip arthroplasty in men (0.91; 95% CI, 0.87-0.95), but not women (0.98; 95% CI, 0.94-1.01). Longer LTL was weakly associated with reduced risk of any incident fracture in women (HR/SD 0.96; 95% CI, 0.93-1.00) with less evidence in men (0.98; 95% CI, 0.93-1.02). Associations with incident outcomes were not materially altered by adjustment for heel eBMD, grip strength, gait speed, fat mass, or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeletal systems might influence later life musculoskeletal outcomes. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).",,doi:https://doi.org/10.1002/jbmr.4664; html:https://europepmc.org/articles/PMC9826022; pdf:https://europepmc.org/articles/PMC9826022?pdf=render 33542327,https://doi.org/10.1038/s41598-021-82214-3,Classification of paediatric brain tumours by diffusion weighted imaging and machine learning.,"Novak J, Zarinabad N, Rose H, Arvanitis T, MacPherson L, Pinkey B, Oates A, Hales P, Grundy R, Auer D, Gutierrez DR, Jaspan T, Avula S, Abernethy L, Kaur R, Hargrave D, Mitra D, Bailey S, Davies N, Clark C, Peet A.",,Scientific reports,2021,2021-02-04,Y,,,,"To determine if apparent diffusion coefficients (ADC) can discriminate between posterior fossa brain tumours on a multicentre basis. A total of 124 paediatric patients with posterior fossa tumours (including 55 Medulloblastomas, 36 Pilocytic Astrocytomas and 26 Ependymomas) were scanned using diffusion weighted imaging across 12 different hospitals using a total of 18 different scanners. Apparent diffusion coefficient maps were produced and histogram data was extracted from tumour regions of interest. Total histograms and histogram metrics (mean, variance, skew, kurtosis and 10th, 20th and 50th quantiles) were used as data input for classifiers with accuracy determined by tenfold cross validation. Mean ADC values from the tumour regions of interest differed between tumour types, (ANOVA P < 0.001). A cut off value for mean ADC between Ependymomas and Medulloblastomas was found to be of 0.984 × 10-3 mm2 s-1 with sensitivity 80.8% and specificity 80.0%. Overall classification for the ADC histogram metrics were 85% using Naïve Bayes and 84% for Random Forest classifiers. The most commonly occurring posterior fossa paediatric brain tumours can be classified using Apparent Diffusion Coefficient histogram values to a high accuracy on a multicentre basis.",,doi:https://doi.org/10.1038/s41598-021-82214-3; html:https://europepmc.org/articles/PMC7862387; pdf:https://europepmc.org/articles/PMC7862387?pdf=render -32781946,https://doi.org/10.1098/rspb.2020.1405,Key questions for modelling COVID-19 exit strategies.,"Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.",,Proceedings. Biological sciences,2020,2020-08-12,Y,Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2,,,"Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.",,doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render 35184736,https://doi.org/10.1186/s12916-022-02271-x,Comparative assessment of methods for short-term forecasts of COVID-19 hospital admissions in England at the local level.,"Meakin S, Abbott S, Bosse N, Munday J, Gruson H, Hellewell J, Sherratt K, CMMID COVID-19 Working Group, Funk S.",,BMC medicine,2022,2022-02-21,Y,Forecasting; Infectious disease; outbreak; Real-time; Ensemble; Healthcare Demand; Covid-19,,,"

Background

Forecasting healthcare demand is essential in epidemic settings, both to inform situational awareness and facilitate resource planning. Ideally, forecasts should be robust across time and locations. During the COVID-19 pandemic in England, it is an ongoing concern that demand for hospital care for COVID-19 patients in England will exceed available resources.

Methods

We made weekly forecasts of daily COVID-19 hospital admissions for National Health Service (NHS) Trusts in England between August 2020 and April 2021 using three disease-agnostic forecasting models: a mean ensemble of autoregressive time series models, a linear regression model with 7-day-lagged local cases as a predictor, and a scaled convolution of local cases and a delay distribution. We compared their point and probabilistic accuracy to a mean-ensemble of them all and to a simple baseline model of no change from the last day of admissions. We measured predictive performance using the weighted interval score (WIS) and considered how this changed in different scenarios (the length of the predictive horizon, the date on which the forecast was made, and by location), as well as how much admissions forecasts improved when future cases were known.

Results

All models outperformed the baseline in the majority of scenarios. Forecasting accuracy varied by forecast date and location, depending on the trajectory of the outbreak, and all individual models had instances where they were the top- or bottom-ranked model. Forecasts produced by the mean-ensemble were both the most accurate and most consistently accurate forecasts amongst all the models considered. Forecasting accuracy was improved when using future observed, rather than forecast, cases, especially at longer forecast horizons.

Conclusions

Assuming no change in current admissions is rarely better than including at least a trend. Using confirmed COVID-19 cases as a predictor can improve admissions forecasts in some scenarios, but this is variable and depends on the ability to make consistently good case forecasts. However, ensemble forecasts can make forecasts that make consistently more accurate forecasts across time and locations. Given minimal requirements on data and computation, our admissions forecasting ensemble could be used to anticipate healthcare needs in future epidemic or pandemic settings.",,doi:https://doi.org/10.1186/s12916-022-02271-x; html:https://europepmc.org/articles/PMC8858706; pdf:https://europepmc.org/articles/PMC8858706?pdf=render -32692755,https://doi.org/10.1371/journal.pone.0236193,A genetic model of ivabradine recapitulates results from randomized clinical trials.,"Legault MA, Sandoval J, Provost S, Barhdadi A, Lemieux Perreault LP, Shah S, Lumbers RT, de Denus S, Tyl B, Tardif JC, Dubé MP.",,PloS one,2020,2020-07-21,Y,,,,"

Background

Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints.

Methods

We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.

Results

Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 ×10-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61).

Conclusion

Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.",,doi:https://doi.org/10.1371/journal.pone.0236193; html:https://europepmc.org/articles/PMC7373274; pdf:https://europepmc.org/articles/PMC7373274?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0236193&type=printable +32781946,https://doi.org/10.1098/rspb.2020.1405,Key questions for modelling COVID-19 exit strategies.,"Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.",,Proceedings. Biological sciences,2020,2020-08-12,Y,Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2,,,"Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.",,doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render 31220083,https://doi.org/10.1371/journal.pmed.1002833,Associations of genetically determined iron status across the phenome: A mendelian randomization study.,"Gill D, Benyamin B, Moore LSP, Monori G, Zhou A, Koskeridis F, Evangelou E, Laffan M, Walker AP, Tsilidis KK, Dehghan A, Elliott P, Hyppönen E, Tzoulaki I.",,PLoS medicine,2019,2019-06-20,Y,,Understanding the Causes of Disease,,"

Background

Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.

Methods and findings

Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation [SD] increase in genetically determined serum iron levels 0.72, 95% confidence interval [CI] 0.64-0.81, P = 4 × 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 × 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 × 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.

Conclusions

Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.",,doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render +32692755,https://doi.org/10.1371/journal.pone.0236193,A genetic model of ivabradine recapitulates results from randomized clinical trials.,"Legault MA, Sandoval J, Provost S, Barhdadi A, Lemieux Perreault LP, Shah S, Lumbers RT, de Denus S, Tyl B, Tardif JC, Dubé MP.",,PloS one,2020,2020-07-21,Y,,,,"

Background

Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints.

Methods

We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.

Results

Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 ×10-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61).

Conclusion

Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.",,doi:https://doi.org/10.1371/journal.pone.0236193; html:https://europepmc.org/articles/PMC7373274; pdf:https://europepmc.org/articles/PMC7373274?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0236193&type=printable 32807724,https://doi.org/10.1016/j.auec.2020.07.007,Pain assessment following burn injury in Australia and New Zealand: Variation in practice and its association on in-hospital outcomes.,"Tracy LM, Cleland H, Cameron PA, Gabbe BJ.",,Australasian emergency care,2021,2020-08-15,N,Australia; Burn; Pain; New Zealand; Registry; Pain Assessment,,,"

Background

Pain is common following burn injury. Pain assessments are required to ensure appropriate pain management is provided. This study aimed to describe the prevalence and potential variation in practice of validated and documented pain assessment following burn injury in Australian and New Zealand burn units, identify clinical characteristics of patients who receive a pain assessment, and explore the associations between receiving a pain assessment and in-hospital outcomes.

Methods

Burns Registry of Australia and New Zealand (BRANZ) admissions data were extracted. Responses to the pain assessment field were presented by contributing burns unit using frequencies and percentages. Demographic, injury severity and event, and in-hospital outcomes data were assessed.

Results

There were 3009 admissions over the study period; 2481 of these received an assessment. The rate of pain assessment varied considerably between units. Women and adult patients more commonly received a pain assessment. Receiving a pain assessment was associated with a 53% adjusted increase in LOS.

Conclusions

There are differences in the profile of patients who receive a pain assessment after burn injury. The findings of this study will be reported back to designated burns units to improve pain assessment rates and patient care.",,doi:https://doi.org/10.1016/j.auec.2020.07.007 37208429,https://doi.org/10.1038/s41598-023-33391-w,Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.,"Zöllner J, Finer S, Linton KJ, Genes and Health Research Team, van Heel DA, Williamson C, Dixon PH.",,Scientific reports,2023,2023-05-19,Y,,,,"This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.",,doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render; doi:https://doi.org/10.1038/s41598-023-33391-w 33659712,https://doi.org/10.12688/wellcomeopenres.16431.2,Healthcare use by people who use illicit opioids (HUPIO): development of a cohort based on electronic primary care records in England.,"Lewer D, Padmanathan P, Qummer Ul Arfeen M, Denaxas S, Forbes H, Gonzalez-Izquierdo A, Hickman M.",,Wellcome open research,2020,2020-01-01,Y,Drug dependence; Illicit Drugs; Substance Use Disorders; Electronic Health Records; Opioid Agonist Therapy,,,"Background: People who use illicit opioids such as heroin have substantial health needs, but there are few longitudinal studies of general health and healthcare in this population. Most research to date has focused on a narrow set of outcomes, including overdoses and HIV or hepatitis infections. We developed and validated a cohort using UK primary care electronic health records (Clinical Practice Research Datalink GOLD and AURUM databases) to facilitate research into healthcare use by people who use illicit opioid use (HUPIO). Methods: Participants are patients in England with primary care records indicating a history of illicit opioid use. We identified codes including prescriptions of opioid agonist therapies (methadone and buprenorphine) and clinical observations such as 'heroin dependence'. We constructed a cohort of patients with at least one of these codes and aged 18-64 at cohort entry, with follow-up between January 1997 and March 2020. We validated the cohort by comparing patient characteristics and mortality rates to other cohorts of people who use illicit opioids, with different recruitment methods. Results: Up to March 2020, the HUPIO cohort included 138,761 patients with a history of illicit opioid use. Demographic characteristics and all-cause mortality were similar to existing cohorts: 69% were male; the median age at index for patients in CPRD AURUM (the database with more included participants) was 35.3 (interquartile range 29.1-42.6); the average age of new cohort entrants increased over time; 76% had records indicating current tobacco smoking; patients disproportionately lived in deprived neighbourhoods; and all-cause mortality risk was 6.6 (95% CI 6.5-6.7) times the general population of England. Conclusions: Primary care data offer new opportunities to study holistic health outcomes and healthcare of this population. The large sample enables investigation of rare outcomes, whilst the availability of linkage to external datasets allows investigation of hospital use, cancer treatment, and mortality.",,doi:https://doi.org/10.12688/wellcomeopenres.16431.2; html:https://europepmc.org/articles/PMC7901498; pdf:https://europepmc.org/articles/PMC7901498?pdf=render @@ -1476,8 +1478,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35279265,https://doi.org/10.1016/s2213-2600(21)00511-7,"Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis.","Adeloye D, Song P, Zhu Y, Campbell H, Sheikh A, Rudan I, NIHR RESPIRE Global Respiratory Health Unit.",,The Lancet. Respiratory medicine,2022,2022-03-10,Y,,,,"

Background

Chronic obstructive pulmonary disease (COPD) is an increasingly important cause of morbidity, disability, and mortality worldwide. We aimed to estimate global, regional, and national COPD prevalence and risk factors to guide policy and population interventions.

Methods

For this systematic review and modelling study, we searched MEDLINE, Embase, Global Health, and CINAHL, for population-based studies on COPD prevalence published between Jan 1, 1990, and Dec 31, 2019. We included data reported using the two main case definitions: the Global Initiative for Chronic Obstructive Lung Disease fixed ratio (GOLD; FEV1/FVC<0·7) and the lower limit of normal (LLN; FEV1/FVCFindingsWe identified 162 articles reporting population-based studies conducted across 260 sites in 65 countries. In 2019, the global prevalence of COPD among people aged 30-79 years was 10·3% (95% CI 8·2-12·8) using the GOLD case definition, which translates to 391·9 million people (95% CI 312·6-487·9), and 7·6% (5·8-10·1) using the LLN definition, which translates to 292·0 million people (219·8-385·6). Using the GOLD definition, we estimated that 391·9 million (95% CI 312·6-487·9) people aged 30-79 years had COPD worldwide in 2019, with most (315·5 million [246·7-399·6]; 80·5%) living in LMICs. The overall prevalence of GOLD-COPD among people aged 30-79 years was the highest in the Western Pacific region (11·7% [95% CI 9·3-14·6]) and lowest in the region of the Americas (6·8% [95% CI 5·6-8·2]). Globally, male sex (OR 2·1 [95% CI 1·8-2·3]), smoking (current smoker 3·2 [2·5-4·0]; ever smoker 2·3 [2·0-2·5]), body-mass index of less than 18·5 kg/m2 (2·2 [1·7-2·7]), biomass exposure (1·4 [1·2-1·7]), and occupational exposure to dust or smoke (1·4 [1·3-1·6]) were all substantial risk factors for COPD.

Interpretation

With more than three-quarters of global COPD cases in LMICs, tackling this chronic condition is a major and increasing challenge for health systems in these settings. In the absence of targeted population-wide efforts and health system reforms in these settings, many of which are under-resourced, achieving a substantial reduction in the burden of COPD globally might remain a difficult task.

Funding

National Institute for Health Research and Health Data Research UK.",,doi:https://doi.org/10.1016/S2213-2600(21)00511-7; html:https://europepmc.org/articles/PMC9050565 30585256,https://doi.org/10.1038/s41416-018-0365-6,"Personal radio use and cancer risks among 48,518 British police officers and staff from the Airwave Health Monitoring Study.","Gao H, Aresu M, Vergnaud AC, McRobie D, Spear J, Heard A, Kongsgård HW, Singh D, Muller DC, Elliott P.",,British journal of cancer,2019,2018-12-26,Y,,Understanding the Causes of Disease,,"

Background

Radiofrequency electromagnetic fields (RF-EMF) from mobile phones have been classified as potentially carcinogenic. No study has investigated use of Terrestrial Trunked Radio (TETRA), a source of RF-EMF with wide occupational use, and cancer risks.

Methods

We investigated association of monthly personal radio use and risk of cancer using Cox proportional hazards regression among 48,518 police officers and staff of the Airwave Health Monitoring Study in Great Britain.

Results

During median follow-up of 5.9 years, 716 incident cancer cases were identified. Among users, the median of the average monthly duration of use in the year prior to enrolment was 30.5  min (inter-quartile range 8.1, 68.1). Overall, there was no association between personal radio use and risk of all cancers (hazard ratio [HR] = 0.98, 95% confidence interval [CI]: 0.93, 1.03). For head and neck cancers HR = 0.72 (95% CI: 0.30, 1.70) among personal radio users vs non-users, and among users it was 1.06 (95% CI: 0.91, 1.23) per doubling of minutes of personal radio use.

Conclusions

With the limited follow-up to date, we found no evidence of association of personal radio use with cancer risk. Continued follow-up of the cohort is warranted.",,doi:https://doi.org/10.1038/s41416-018-0365-6; html:https://europepmc.org/articles/PMC6354010; pdf:https://europepmc.org/articles/PMC6354010?pdf=render 33482294,https://doi.org/10.1016/j.jclinepi.2021.01.003,Real-time imputation of missing predictor values improved the application of prediction models in daily practice.,"Nijman SWJ, Groenhof TKJ, Hoogland J, Bots ML, Brandjes M, Jacobs JJL, Asselbergs FW, Moons KGM, Debray TPA.",,Journal of clinical epidemiology,2021,2021-01-19,N,Prediction; Missing Data; Electronic Health Records; Multiple Imputations; Computerized Decision Support System; Real-time Imputation,,,"

Objectives

In clinical practice, many prediction models cannot be used when predictor values are missing. We, therefore, propose and evaluate methods for real-time imputation.

Study design and setting

We describe (i) mean imputation (where missing values are replaced by the sample mean), (ii) joint modeling imputation (JMI, where we use a multivariate normal approximation to generate patient-specific imputations), and (iii) conditional modeling imputation (CMI, where a multivariable imputation model is derived for each predictor from a population). We compared these methods in a case study evaluating the root mean squared error (RMSE) and coverage of the 95% confidence intervals (i.e., the proportion of confidence intervals that contain the true predictor value) of imputed predictor values.

Results

-RMSE was lowest when adopting JMI or CMI, although imputation of individual predictors did not always lead to substantial improvements as compared to mean imputation. JMI and CMI appeared particularly useful when the values of multiple predictors of the model were missing. Coverage reached the nominal level (i.e., 95%) for both CMI and JMI.

Conclusion

Multiple imputations using either CMI or JMI is recommended when dealing with missing predictor values in real-time settings.",,doi:https://doi.org/10.1016/j.jclinepi.2021.01.003 -37542272,https://doi.org/10.1186/s12916-023-02948-x,Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.,"Henderson AD, Adesanya E, Mulick A, Matthewman J, Vu N, Davies F, Smith CH, Hayes J, Mansfield KE, Langan SM.",,BMC medicine,2023,2023-08-04,Y,Depression; Anxiety; Skin Disease; Electronic Health Records,,,"

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.",,doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render 34903266,https://doi.org/10.1186/s13059-021-02561-2,CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation.,"Hu Z, Ahmed AA, Yau C.",,Genome biology,2021,2021-12-13,Y,Clustering; Confounding Factors; Single-cell Rna-seq,,,"Clustering of joint single-cell RNA-Seq (scRNA-Seq) data is often challenged by confounding factors, such as batch effects and biologically relevant variability. Existing batch effect removal methods typically require strong assumptions on the composition of cell populations being near identical across samples. Here, we present CIDER, a meta-clustering workflow based on inter-group similarity measures. We demonstrate that CIDER outperforms other scRNA-Seq clustering methods and integration approaches in both simulated and real datasets. Moreover, we show that CIDER can be used to assess the biological correctness of integration in real datasets, while it does not require the existence of prior cellular annotations.",,doi:https://doi.org/10.1186/s13059-021-02561-2; html:https://europepmc.org/articles/PMC8667531; pdf:https://europepmc.org/articles/PMC8667531?pdf=render +37542272,https://doi.org/10.1186/s12916-023-02948-x,Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.,"Henderson AD, Adesanya E, Mulick A, Matthewman J, Vu N, Davies F, Smith CH, Hayes J, Mansfield KE, Langan SM.",,BMC medicine,2023,2023-08-04,Y,Depression; Anxiety; Skin Disease; Electronic Health Records,,,"

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.",,doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render 34345870,https://doi.org/10.1016/j.bbih.2021.100286,The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach.,"Lee H, Metz A, McDiarmid A, Palmos A, Lee SH, Curtis CJ, Patel H, Newhouse SJ, Thuret S.",,"Brain, behavior, & immunity - health",2021,2021-08-01,Y,Hippocampus; Neurogenesis; Inflammation; Neural stem cells; in vitro model; single nucleotide polymorphisms SNP; Eqtl; Gene Variants,,,"Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.",,doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render 30993728,https://doi.org/10.1111/cen.13990,Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease.,"Toulis KA, Viola D, Gkoutos G, Keerthy D, Boelaert K, Nirantharakumar K.",,Clinical endocrinology,2019,2019-05-17,N,Atrial fibrillation; Cardiovascular events; Thyroid cancer; Differentiated Thyroid Carcinoma,,,"

Context

The incidence of differentiated thyroid cancer (DTC) is increasing, yet the prognosis is favourable and long-term survival is expected. Exogenous TSH suppression has been used for many years to prevent DTC recurrence and may be associated with increased risks of circulatory diseases.

Design

Risks of circulatory disease in patients treated for DTC were compared to randomly matched patients without DTC (controls) up to a 1:5 ratio using age, sex, body mass index (BMI) and smoking as the matching parameters in a population-based, open cohort study using The Health Improvement Network.

Patients

A total of 3009 patients treated for DTC with no pre-existing cardiovascular disease were identified and matched to 11 303 controls, followed up to median of 5 years.

Results

A total of 1259 incident circulatory events were recorded during the observation period. No difference in the risk of ischaemic heart disease (IHD) (adjusted hazards ratio [aHR]: 1.04, 95% CI: 0.80-1.36) or heart failure (HF) (aHR: 1.27, 95% CI: 0.89-1.81) was detected. The risk of atrial fibrillation (AF) and stroke was significantly higher in patients with DTC (aHR: 1.71, 95% CI: 1.36-2.15 and aHR: 1.34, 95% CI: 1.05-1.72, respectively). In a sensitivity analysis limited to newly diagnosed patients with DTC, only the risk of AF was consistently elevated (aHR: 1.86, 95% CI: 1.33-2.60).

Conclusions

The increased risk of AF in patients who have undergone treatment for DTC but without pre-existing CVD may warrant periodic screening for this arrhythmia. Whereas no evidence of increased risk of IHD or HF was observed, the increased risk of stroke/TIA warrants further investigation.",,doi:https://doi.org/10.1111/cen.13990 32346541,https://doi.org/10.1093/burnst/tkz004,Predictors of itch and pain in the 12 months following burn injury: results from the Burns Registry of Australia and New Zealand (BRANZ) Long-Term Outcomes Project.,"Tracy LM, Edgar DW, Schrale R, Cleland H, Gabbe BJ, BRANZ Adult Long-Term Outcomes Pilot Project participating sites and working party.",,Burns & trauma,2020,2020-02-27,Y,Australia; Pain; New Zealand; Cohort study; Outcomes; Predictor; Itch; Burn Registry,Better Care,injuries and accidents,"

Background

Itch and pain are common complaints of patients with burn injuries. This study aimed to describe the prevalence and predictors of itch and moderate to severe pain in the first 12 months following a burn injury, and determine the association between itch, moderate to severe pain, work-related outcomes, and health-related quality of life following a burn injury.

Methods

Burn patients aged 18 years and older were recruited from five Australian specialist burn units. Patients completed the 36-item Short Form Health Survey Version 2 (SF-36 V2), the Sickness Impact Profile (SIP) work scale, and a specially developed questionnaire relating to itch at 1, 6, and 12 months post-injury. Moderate to severe pain was defined as a score less than 40 on the bodily pain domain of the SF-36 V2. Multivariate mixed-effects regression models were used to identify patient and burn injury predictors of itch and moderate to severe pain.

Results

Three hundred and twenty-eight patients were included. The prevalence of itch decreased from 50% at 1 month to 27% at 12 months. Similarly, the prevalence of moderate to severe pain decreased from 23% at 1 month to 13% at 12 months. Compared to patients aged 18-34, the adjusted odds of experiencing any itch were 59% (95% CI: 0.20, 0.82) and 55% (95% CI: 0.22, 0.91) lower for patients aged between 35 and 49 and ≥ 50 years, respectively. Compared to patients aged 18-34, the adjusted odds of experiencing moderate to severe pain were 3.12 (95% CI: 1.35, 7.20) and 3.42 (95% CI: 1.47, 7.93) times higher for patients aged 35-49 and ≥ 50 years, respectively.

Conclusions

Less than 15% of patients reported moderate or severe pain at 12 months, while approximately one-quarter of the patients reported itch at the same period. The presence of moderate to severe pain was associated with a greater negative impact on health-related quality of life and work outcomes compared to itch. Further research is needed to improve our ability to identify patients at higher risk of persistent itch and pain who would benefit from targeted review and intervention studies.",,doi:https://doi.org/10.1093/burnst/tkz004; html:https://europepmc.org/articles/PMC7175773; pdf:https://europepmc.org/articles/PMC7175773?pdf=render @@ -1487,8 +1489,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35386996,https://doi.org/10.3389/falgy.2021.677677,Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?,"Thompson RJ, Sayers I, Kuokkanen K, Hall IP.",,Frontiers in allergy,2021,2021-05-31,Y,Lung; Bioinformatics; Asthma; airway; Gene Expression; purinergic receptor; Purinergic Signaling,,,"Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.",,doi:https://doi.org/10.3389/falgy.2021.677677; html:https://europepmc.org/articles/PMC8974712; pdf:https://europepmc.org/articles/PMC8974712?pdf=render 36998408,https://doi.org/10.3389/fmicb.2023.1070340,A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.,"Smith RP, May HE, AbuOun M, Stubberfield E, Gilson D, Chau KK, Crook DW, Shaw LP, Read DS, Stoesser N, Vilar MJ, Anjum MF.",,Frontiers in microbiology,2023,2023-03-14,Y,Sheep; Cattle; Pigs; Antimicrobial resistance; Longitudinal; Antimicrobial Usage,,,"

Introduction

There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.

Methods

A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.

Results

Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.

Discussion

The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.",,doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render 35251129,https://doi.org/10.3389/fgene.2022.818574,Calculating Polygenic Risk Scores (PRS) in UK Biobank: A Practical Guide for Epidemiologists.,"Collister JA, Liu X, Clifton L.",,Frontiers in genetics,2022,2022-02-18,Y,Polygenic Score; Genetic Risk Score; Uk Biobank; Polygenic Risk Score; Worked Example,,,"A polygenic risk score estimates the genetic risk of an individual for some disease or trait, calculated by aggregating the effect of many common variants associated with the condition. With the increasing availability of genetic data in large cohort studies such as the UK Biobank, inclusion of this genetic risk as a covariate in statistical analyses is becoming more widespread. Previously this required specialist knowledge, but as tooling and data availability have improved it has become more feasible for statisticians and epidemiologists to calculate existing scores themselves for use in analyses. While tutorial resources exist for conducting genome-wide association studies and generating of new polygenic risk scores, fewer guides exist for the simple calculation and application of existing genetic scores. This guide outlines the key steps of this process: selection of suitable polygenic risk scores from the literature, extraction of relevant genetic variants and verification of their quality, calculation of the risk score and key considerations of its inclusion in statistical models, using the UK Biobank imputed data as a model data set. Many of the techniques in this guide will generalize to other datasets, however we also focus on some of the specific techniques required for using data in the formats UK Biobank have selected. This includes some of the challenges faced when working with large numbers of variants, where the computation time required by some tools is impractical. While we have focused on only a couple of tools, which may not be the best ones for every given aspect of the process, one barrier to working with genetic data is the sheer volume of tools available, and the difficulty for a novice to assess their viability. By discussing in depth a couple of tools that are adequate for the calculation even at large scale, we hope to make polygenic risk scores more accessible to a wider range of researchers.",,doi:https://doi.org/10.3389/fgene.2022.818574; html:https://europepmc.org/articles/PMC8894758; pdf:https://europepmc.org/articles/PMC8894758?pdf=render -37006331,https://doi.org/10.1093/braincomms/fcad041,Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.,"Breedon JR, Marshall CR, Giovannoni G, van Heel DA, Genes & Health Research Team , Dobson R, Jacobs BM.",,Brain communications,2023,2023-02-22,Y,Genetics; Multiple sclerosis; Ethnicity,,,"Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of ∼500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.",,doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render 34062542,https://doi.org/10.1159/000517521,Structural Endpoints and Outcome Measures in Uveitis.,"Wintergerst MWM, Liu X, Terheyden JH, Pohlmann D, Li JQ, Montesano G, Ometto G, Holz FG, Crabb DP, Pleyer U, Heinz C, Denniston AK, Finger RP.",,Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde,2021,2021-06-01,N,Biomarker; Uveitis; Outcome; Outcome Measure; Endpoint; Imaging Biomarker; Inflammatory Eye Diseases; Instrument-based Measure,,,"Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and ""core outcomes"" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current ""core modalities"" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.",,doi:https://doi.org/10.1159/000517521 +37006331,https://doi.org/10.1093/braincomms/fcad041,Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.,"Breedon JR, Marshall CR, Giovannoni G, van Heel DA, Genes & Health Research Team , Dobson R, Jacobs BM.",,Brain communications,2023,2023-02-22,Y,Genetics; Multiple sclerosis; Ethnicity,,,"Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of ∼500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.",,doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render 33453763,https://doi.org/10.1016/s2468-1253(21)00005-4,Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.,"Morris EJA, Goldacre R, Spata E, Mafham M, Finan PJ, Shelton J, Richards M, Spencer K, Emberson J, Hollings S, Curnow P, Gair D, Sebag-Montefiore D, Cunningham C, Rutter MD, Nicholson BD, Rashbass J, Landray M, Collins R, Casadei B, Baigent C.",,The lancet. Gastroenterology & hepatology,2021,2021-01-15,Y,,,,"

Background

There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England.

Methods

Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated.

Findings

As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020.

Interpretation

The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England.

Funding

Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.",,doi:https://doi.org/10.1016/S2468-1253(21)00005-4; html:https://europepmc.org/articles/PMC7808901; pdf:https://europepmc.org/articles/PMC7808901?pdf=render 32702311,https://doi.org/10.1016/s1470-2045(20)30392-2,Effect of delays in the 2-week-wait cancer referral pathway during the COVID-19 pandemic on cancer survival in the UK: a modelling study.,"Sud A, Torr B, Jones ME, Broggio J, Scott S, Loveday C, Garrett A, Gronthoud F, Nicol DL, Jhanji S, Boyce SA, Williams M, Riboli E, Muller DC, Kipps E, Larkin J, Navani N, Swanton C, Lyratzopoulos G, McFerran E, Lawler M, Houlston R, Turnbull C.",,The Lancet. Oncology,2020,2020-07-20,Y,,,,"

Background

During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2.

Methods

In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008-17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013-16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I-III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1-6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred.

Findings

Across England in 2013-16, an average of 6281 patients with stage I-III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1-3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3-8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type.

Interpretation

Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer.

Funding

None.",,doi:https://doi.org/10.1016/S1470-2045(20)30392-2; html:https://europepmc.org/articles/PMC7116538; pdf:https://europepmc.org/articles/PMC7116538?pdf=render 31053412,https://doi.org/10.1016/j.burns.2019.04.006,Severe burns in Australian and New Zealand adults: Epidemiology and burn centre care.,"Toppi J, Cleland H, Gabbe B.",,Burns : journal of the International Society for Burn Injuries,2019,2019-04-30,N,Mortality; Burn; Severe burns; epidemiology,,,"

Introduction

Studies describing the epidemiology of severe burns (>20% total body surface area) in adults are limited despite the extensive associated morbidity and mortality. This study aimed to describe the epidemiology of severe burn injuries admitted to burn centres in Australia and New Zealand.

Materials and methods

Data from the Burns Registry of Australia and New Zealand (BRANZ) were used in this study. Patients were eligible for inclusion if they were admitted between August 2009 and June 2013, were adults (18-years or older), and had burns of 20% total body surface area (TBSA) or greater. Demographics, burn characteristics and in-hospital mortality risk factors were investigated using multivariable Cox proportional hazards analysis.

Results

There were 496 BRANZ registered patients who met the inclusion criteria. Over half of the patients were aged 18-40 years and most were male. The median (IQR) TBSA was 31 (25-47). Most (75%) patients had burns involving <50% TBSA, 58% sustained their burn injury at home, and 86% had sustained flame burns. Leisure activities, working for income and preparing food together accounted for over 48% of the activities undertaken at the time of injury. The in-hospital mortality rate was 17% and the median (IQR) length of stay was 24 (12-44) days. Seventy-two percent were admitted to an intensive care unit (ICU) and 40% of patients had an associated inhalation injury. Alcohol and/or drug involvement was suspected in 25% of cases.

Conclusion

This study describes the demographics, burn injury characteristics and in-hospital outcomes of severe burn injuries in adults whilst also identifying key predictors of inpatient mortality. Key findings included the over-representation of young males, intentional self-harm injuries and flame as a cause of burns and highlights high risk groups to help aid in the development of targeted prevention strategies.",,doi:https://doi.org/10.1016/j.burns.2019.04.006 @@ -1507,11 +1509,11 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 33825703,https://doi.org/10.1107/s2059798321000826,Vagabond: bond-based parametrization reduces overfitting for refinement of proteins.,Ginn HM.,,"Acta crystallographica. Section D, Structural biology",2021,2021-03-30,Y,Models; X-ray diffraction; Protein Flexibility; Bonds; Refinement Software,,,"Structural biology methods have delivered over 150 000 high-resolution structures of macromolecules, which have fundamentally altered our understanding of biology and our approach to developing new medicines. However, the description of molecular flexibility is instrinsically flawed and in almost all cases, regardless of the experimental method used for structure determination, there remains a strong overfitting bias during molecular model building and refinement. In the worst case this can lead to wholly incorrect structures and thus incorrect biological interpretations. Here, by reparametrizing the description of these complex structures in terms of bonds rather than atomic positions, and by modelling flexibility using a deterministic ensemble of structures, it is demonstrated that structures can be described using fewer parameters than in conventional refinement. The current implementation, applied to X-ray diffraction data, significantly reduces the extent of overfitting, allowing the experimental data to reveal more biological information in electron-density maps.",,doi:https://doi.org/10.1107/S2059798321000826; html:https://europepmc.org/articles/PMC8025884; pdf:https://europepmc.org/articles/PMC8025884?pdf=render 33782080,https://doi.org/10.1136/thoraxjnl-2020-216512,Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.,"Shah SA, Quint JK, Nwaru BI, Sheikh A.",,Thorax,2021,2021-03-29,Y,Asthma; Asthma Epidemiology; Covid-19,,,"

Background

The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods

We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results

From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions

There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.",,doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render; pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf 36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

Methods and analysis

Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

Ethics and dissemination

Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

Trial registration number

NCT05240742.",,doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render -34632432,https://doi.org/10.1016/s2666-5247(21)00128-2,Epidemiology of Mycobacterium abscessus in England: an observational study.,"Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.",,The Lancet. Microbe,2021,2021-10-01,Y,,,,"

Background

Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.

Methods

In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).

Findings

2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.

Interpretation

Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.

Funding

The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.",,doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905 31363735,https://doi.org/10.1093/hmg/ddz187,Towards clinical utility of polygenic risk scores.,"Lambert SA, Abraham G, Inouye M.",,Human molecular genetics,2019,2019-11-01,N,,,,"Prediction of disease risk is an essential part of preventative medicine, often guiding clinical management. Risk prediction typically includes risk factors such as age, sex, family history of disease and lifestyle (e.g. smoking status); however, in recent years, there has been increasing interest to include genomic information into risk models. Polygenic risk scores (PRS) aggregate the effects of many genetic variants across the human genome into a single score and have recently been shown to have predictive value for multiple common diseases. In this review, we summarize the potential use cases for seven common diseases (breast cancer, prostate cancer, coronary artery disease, obesity, type 1 diabetes, type 2 diabetes and Alzheimer's disease) where PRS has or could have clinical utility. PRS analysis for these diseases frequently revolved around (i) risk prediction performance of a PRS alone and in combination with other non-genetic risk factors, (ii) estimation of lifetime risk trajectories, (iii) the independent information of PRS and family history of disease or monogenic mutations and (iv) estimation of the value of adding a PRS to specific clinical risk prediction scenarios. We summarize open questions regarding PRS usability, ancestry bias and transferability, emphasizing the need for the next wave of studies to focus on the implementation and health-economic value of PRS testing. In conclusion, it is becoming clear that PRS have value in disease risk prediction and there are multiple areas where this may have clinical utility.",,doi:https://doi.org/10.1093/hmg/ddz187 +34632432,https://doi.org/10.1016/s2666-5247(21)00128-2,Epidemiology of Mycobacterium abscessus in England: an observational study.,"Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.",,The Lancet. Microbe,2021,2021-10-01,Y,,,,"

Background

Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.

Methods

In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).

Findings

2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.

Interpretation

Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.

Funding

The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.",,doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905 32619549,https://doi.org/10.1016/j.cels.2020.05.012,Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger AS, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Suttorp N, Witzenrath M, Kurth F, Sander LE, Ralser M.",,Cell systems,2020,2020-06-02,Y,Mass spectrometry; High-throughput Proteomics; Swath-ms; Antiviral Immune Response; Clinical Classifiers; Covid-19 Infection,,,"The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.",,doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033 -35751107,https://doi.org/10.1186/s13059-022-02702-1,Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.,"Zhang P, Amarasinghe HE, Whalley JP, Tay C, Fang H, Migliorini G, Brown AC, Allcock A, Scozzafava G, Rath P, Davies B, Knight JC.",,Genome biology,2022,2022-06-24,Y,,,,"

Background

Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.

Results

We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NFκB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.

Conclusions

Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.",,doi:https://doi.org/10.1186/s13059-022-02702-1; html:https://europepmc.org/articles/PMC9229144; pdf:https://europepmc.org/articles/PMC9229144?pdf=render 34661196,https://doi.org/10.1093/ehjopen/oeab019,Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.,"Wall C, Huang Y, Le EPV, Ćorović A, Uy CP, Gopalan D, Ma C, Manavaki R, Fryer TD, Aloj L, Graves MJ, Tombetti E, Ariff B, Bambrough P, Hoole SP, Rusk RA, Jayne DR, Dweck MR, Newby D, Fayad ZA, Bennett MR, Peters JE, Slomka P, Dey D, Mason JC, Rudd JHF, Tarkin JM.",,European heart journal open,2021,2021-08-06,Y,coronary artery disease; Takayasu Arteritis; Pericoronary Adipose Tissue Density,,,"

Aims

To examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.

Methods and results

PCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P < 0.0001; PAAT: P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P < 0.0001) and was higher in active vs. inactive TAK (P = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.

Conclusions

PCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.",,doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render +35751107,https://doi.org/10.1186/s13059-022-02702-1,Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.,"Zhang P, Amarasinghe HE, Whalley JP, Tay C, Fang H, Migliorini G, Brown AC, Allcock A, Scozzafava G, Rath P, Davies B, Knight JC.",,Genome biology,2022,2022-06-24,Y,,,,"

Background

Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.

Results

We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NFκB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.

Conclusions

Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.",,doi:https://doi.org/10.1186/s13059-022-02702-1; html:https://europepmc.org/articles/PMC9229144; pdf:https://europepmc.org/articles/PMC9229144?pdf=render 35913736,https://doi.org/10.1093/ehjqcco/qcac045,Impact of cancer diagnosis on distribution and trends of cardiovascular hospitalizations in the USA between 2004 and 2017.,"Kobo O, Raisi-Estabragh Z, Gevaert S, Rana JS, Van Spall HGC, Roguin A, Petersen SE, Ky B, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-10-01,N,Prognosis; trends; Cardio- Oncology,,,"

Background and aims

There is limited data on temporal trends of cardiovascular hospitalizations and outcomes amongst cancer patients. We describe the distribution, trends of admissions, and in-hospital mortality associated with key cardiovascular diseases among cancer patients in the USA between 2004 and 2017.

Methods

Using the Nationwide Inpatient Sample we, identified admissions with five cardiovascular diseases of interest: acute myocardial infarction (AMI), pulmonary embolism (PE), ischaemic stroke, heart failure, atrial fibrillation (AF) or atrial flutter, and intracranial haemorrhage. Patients were stratified by cancer status and type. We estimated crude annual rates of hospitalizations and annual in-hospital all-cause mortality rates.

Results

From >42.5 million hospitalizations with a primary cardiovascular diagnosis, 1.9 million (4.5%) had a concurrent record of cancer. Between 2004 and 2017, cardiovascular admission rates increased by 23.2% in patients with cancer, whilst decreasing by 10.9% in patients without cancer. The admission rate increased among cancer patients across all admission causes and cancer types except prostate cancer. Patients with haematological (9.7-13.5), lung (7.4-8.9), and GI cancer (4.6-6.3) had the highest crude rates of cardiovascular hospitalizations per 100 000 US population. Heart failure was the most common reason for cardiovascular admission in patients across all cancer types, except GI cancer (crude admission rates of 13.6-16.6 per 100 000 US population for patients with cancer).

Conclusions

In contrast to declining trends in patients without cancer, primary cardiovascular admissions in patients with cancer is increasing. The highest admission rates are in patients with haematological cancer, and the most common cause of admission is heart failure.",,doi:https://doi.org/10.1093/ehjqcco/qcac045; html:https://europepmc.org/articles/PMC9603542; pdf:https://europepmc.org/articles/PMC9603542?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac045; pdf:https://biblio.ugent.be/publication/01GTEZMFA3PQ4FR2HWVVMJE1PP/file/01GTEZP5YQ68PC7TFPP52TS6QR.pdf 34737870,https://doi.org/10.7189/jogh.11.15003,Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade.,"Adeloye D, Agarwal D, Barnes PJ, Bonay M, van Boven JF, Bryant J, Caramori G, Dockrell D, D'Urzo A, Ekström M, Erhabor G, Esteban C, Greene CM, Hurst J, Juvekar S, Khoo EM, Ko FW, Lipworth B, López-Campos JL, Maddocks M, Mannino DM, Martinez FJ, Martinez-Garcia MA, McNamara RJ, Miravitlles M, Pinnock H, Pooler A, Quint JK, Schwarz P, Slavich GM, Song P, Tai A, Watz H, Wedzicha JA, Williams MC, Campbell H, Sheikh A, Rudan I.",,Journal of global health,2021,2021-10-09,Y,,,,"

Background

The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD.

Methods

We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities.

Results

62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity.

Conclusions

The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.",,doi:https://doi.org/10.7189/jogh.11.15003; html:https://europepmc.org/articles/PMC8542376; pdf:https://europepmc.org/articles/PMC8542376?pdf=render 35907789,https://doi.org/10.1186/s12859-022-04838-0,fcfdr: an R package to leverage continuous and binary functional genomic data in GWAS.,"Hutchinson A, Liley J, Wallace C.",,BMC bioinformatics,2022,2022-07-30,Y,Functional genomics; Power; FDR; Gwas; Multiple Testing,,,"

Background

Genome-wide association studies (GWAS) are limited in power to detect associations that exceed the stringent genome-wide significance threshold. This limitation can be alleviated by leveraging relevant auxiliary data, such as functional genomic data. Frameworks utilising the conditional false discovery rate have been developed for this purpose, and have been shown to increase power for GWAS discovery whilst controlling the false discovery rate. However, the methods are currently only applicable for continuous auxiliary data and cannot be used to leverage auxiliary data with a binary representation, such as whether SNPs are synonymous or non-synonymous, or whether they reside in regions of the genome with specific activity states.

Results

We describe an extension to the cFDR framework for binary auxiliary data, called ""Binary cFDR"". We demonstrate FDR control of our method using detailed simulations, and show that Binary cFDR performs better than a comparator method in terms of sensitivity and FDR control. We introduce an all-encompassing user-oriented CRAN R package ( https://annahutch.github.io/fcfdr/ ; https://cran.r-project.org/web/packages/fcfdr/index.html ) and demonstrate its utility in an application to type 1 diabetes, where we identify additional genetic associations.

Conclusions

Our all-encompassing R package, fcfdr, serves as a comprehensive toolkit to unite GWAS and functional genomic data in order to increase statistical power to detect genetic associations.",,doi:https://doi.org/10.1186/s12859-022-04838-0; html:https://europepmc.org/articles/PMC9338519; pdf:https://europepmc.org/articles/PMC9338519?pdf=render @@ -1525,8 +1527,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35728939,https://doi.org/10.1136/archdischild-2021-323681,Reductions in hospital care among clinically vulnerable children aged 0-4 years during the COVID-19 pandemic.,"Etoori D, Harron KL, Mc Grath-Lone L, Verfürden ML, Gilbert R, Blackburn R.",,Archives of disease in childhood,2022,2022-06-21,Y,Child Health; Health Services Research; Healthcare Disparities; Covid-19,,,"

Objective

To quantify reductions in hospital care for clinically vulnerable children during the COVID-19 pandemic.

Design

Birth cohort.

Setting

National Health Service hospitals in England.

Study population

All children aged <5 years with a birth recorded in hospital administrative data (January 2010-March 2021).

Main exposure

Clinical vulnerability defined by a chronic health condition, preterm birth (<37 weeks' gestation) or low birth weight (<2500 g).

Main outcomes

Reductions in care defined by predicted hospital contact rates for 2020, estimated from 2015 to 2019, minus observed rates per 1000 child years during the first year of the pandemic (March 2020-2021).

Results

Of 3 813 465 children, 17.7% (one in six) were clinically vulnerable (9.5% born preterm or low birth weight, 10.3% had a chronic condition). Reductions in hospital care during the pandemic were much higher for clinically vulnerable children than peers: respectively, outpatient attendances (314 vs 73 per 1000 child years), planned admissions (55 vs 10) and unplanned admissions (105 vs 79). Clinically vulnerable children accounted for 50.1% of the reduction in outpatient attendances, 55.0% in planned admissions and 32.8% in unplanned hospital admissions. During the pandemic, weekly rates of planned care returned to prepandemic levels for infants with chronic conditions but not older children. Reductions in care differed by ethnic group and level of deprivation. Virtual outpatient attendances increased from 3.2% to 24.8% during the pandemic.

Conclusion

One in six clinically vulnerable children accounted for one-third to one half of the reduction in hospital care during the pandemic.",,doi:https://doi.org/10.1136/archdischild-2021-323681; html:https://europepmc.org/articles/PMC9271837; pdf:https://europepmc.org/articles/PMC9271837?pdf=render; pdf:https://adc.bmj.com/content/archdischild/107/10/e31.full.pdf 33043790,https://doi.org/10.1177/0141076820961776,Advancing UK regulatory science and innovation in healthcare.,"Calvert MJ, Marston E, Samuels M, Rivera SC, Torlinska B, Oliver K, Denniston AK, Hoare S.",,Journal of the Royal Society of Medicine,2021,2020-10-12,Y,,,,,,doi:https://doi.org/10.1177/0141076820961776; html:https://europepmc.org/articles/PMC7809339; pdf:https://europepmc.org/articles/PMC7809339?pdf=render 32685697,https://doi.org/10.12688/wellcomeopenres.15788.1,The contribution of pre-symptomatic infection to the transmission dynamics of COVID-2019.,"Liu Y, Centre for Mathematical Modelling of Infectious Diseases nCoV Working Group, Funk S, Flasche S.",,Wellcome open research,2020,2020-04-01,Y,Incubation period; Serial Interval; Covid-19; Pre-symptomatic Transmission,,,"Background: Pre-symptomatic transmission can be a key determinant of the effectiveness of containment and mitigation strategies for infectious diseases, particularly if interventions rely on syndromic case finding. For COVID-19, infections in the absence of apparent symptoms have been reported frequently alongside circumstantial evidence for asymptomatic or pre-symptomatic transmission. We estimated the potential contribution of pre-symptomatic cases to COVID-19 transmission. Methods: Using the probability for symptom onset on a given day inferred from the incubation period, we attributed the serial interval reported from Shenzen, China, into likely pre-symptomatic and symptomatic transmission. We used the serial interval derived for cases isolated more than 6 days after symptom onset as the no active case finding scenario and the unrestricted serial interval as the active case finding scenario. We reported the estimate assuming no correlation between the incubation period and the serial interval alongside a range indicating alternative assumptions of positive and negative correlation. Results: We estimated that 23% (range accounting for correlation: 12 - 28%) of transmissions in Shenzen may have originated from pre-symptomatic infections. Through accelerated case isolation following symptom onset, this percentage increased to 46% (21 - 46%), implying that about 35% of secondary infections among symptomatic cases have been prevented. These results were robust to using reported incubation periods and serial intervals from other settings. Conclusions: Pre-symptomatic transmission may be essential to consider for containment and mitigation strategies for COVID-19.",,doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render -35849350,https://doi.org/10.1093/nar/gkac612,Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.,"Chen J, Cheng J, Chen X, Inoue M, Liu Y, Song CX.",,Nucleic acids research,2022,2022-10-01,Y,,,,"Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2× depth, we discovered a significant proportion of CpG sites that were not covered in previous 27.5× short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.",,doi:https://doi.org/10.1093/nar/gkac612; html:https://europepmc.org/articles/PMC9561279; pdf:https://europepmc.org/articles/PMC9561279?pdf=render 31234639,https://doi.org/10.1161/circulationaha.118.038814,Use of Genetic Variants Related to Antihypertensive Drugs to Inform on Efficacy and Side Effects.,"Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki I.",,Circulation,2019,2019-06-25,Y,Antihypertensive drugs; Mendelian Randomization Analysis,"Better Care, The Human Phenome",,"

Background

Drug effects can be investigated through natural variation in the genes for their protein targets. The present study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are among the most commonly used medications worldwide.

Methods

Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure at genome-wide significance. Mendelian randomization estimates for drug effects on coronary heart disease and stroke risk were compared with randomized, controlled trial results. A phenome-wide association study in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University biobank (BioVU) and in observational analysis of the UK Biobank.

Results

Suitable genetic proxies for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers (CCBs) were identified. Mendelian randomization estimates for their effect on coronary heart disease and stroke risk, respectively, were comparable to results from randomized, controlled trials against placebo. A phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio, 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (odds ratio, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (hazard ratio, 1.04; 95% CI, 0.83-1.32).

Conclusions

Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.",,doi:https://doi.org/10.1161/CIRCULATIONAHA.118.038814; html:https://europepmc.org/articles/PMC6687408; pdf:https://europepmc.org/articles/PMC6687408?pdf=render +35849350,https://doi.org/10.1093/nar/gkac612,Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.,"Chen J, Cheng J, Chen X, Inoue M, Liu Y, Song CX.",,Nucleic acids research,2022,2022-10-01,Y,,,,"Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2× depth, we discovered a significant proportion of CpG sites that were not covered in previous 27.5× short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.",,doi:https://doi.org/10.1093/nar/gkac612; html:https://europepmc.org/articles/PMC9561279; pdf:https://europepmc.org/articles/PMC9561279?pdf=render 32212911,https://doi.org/10.1161/jaha.119.013684,Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).,"Kaura A, Arnold AD, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Lefroy DC, Francis DP, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet J.",,Journal of the American Heart Association,2020,2020-03-26,Y,Troponin; Mortality; Atrial fibrillation; coronary artery disease; angiography,,,"Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow-up of 1462 (interquartile range, 929-1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01-1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9-3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42-0.89; P=0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.",,doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render 31657946,https://doi.org/10.1164/rccm.201903-0673oc,Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study.,"Maiden MJ, Cameron PA, Rosenfeld JV, Cooper DJ, McLellan S, Gabbe BJ.",,American journal of respiratory and critical care medicine,2020,2020-01-01,N,Elderly; Brain trauma; Functional Performance; Critical Care Outcomes,,,"Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.",,doi:https://doi.org/10.1164/rccm.201903-0673OC 33941991,https://doi.org/10.1016/j.rse.2021.112339,"Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas.","Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati M.",,Remote sensing of environment,2021,2021-05-01,Y,Segmentation; Satellite Images; Convolutional Neural Networks; Street-Level Images; Urban Measurements,,,"Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3 m × 3 m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.",,doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render @@ -1540,9 +1542,9 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 32623924,https://doi.org/10.1161/hypertensionaha.119.14302,Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality Among 398 628 Individuals in UK Biobank.,"Elliott P, Muller DC, Schneider-Luftman D, Pazoki R, Evangelou E, Dehghan A, Neal B, Tzoulaki I.",,"Hypertension (Dallas, Tex. : 1979)",2020,2020-07-06,N,Cardiovascular diseases; Mortality; Blood pressure; risk,,,"We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.",,doi:https://doi.org/10.1161/HYPERTENSIONAHA.119.14302 33021418,https://doi.org/10.1080/09273948.2020.1799038,Noninvasive Instrument-based Tests for Detecting and Measuring Vitreous Inflammation in Uveitis: A Systematic Review.,"Liu X, Hui BT, Way C, Beese S, Adriano A, Keane PA, Moore DJ, Denniston AK.",,Ocular immunology and inflammation,2022,2020-10-06,Y,Imaging; Diagnostic test; Systematic review; Vitreous; ultrasound; Uveitis; optical coherence tomography; Vitritis; Retinal Photography; Vitreous Inflammation,,,"

Purpose

This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading.

Methods

Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted.

Results

Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies.

Conclusion

Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.",,doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?pdf=render 36962800,https://doi.org/10.1371/journal.pgph.0000843,Effect of the COVID-19 pandemic on health service utilization across regions of Ethiopia: An interrupted time series analysis of health information system data from 2019-2020.,"Mebratie AD, Nega A, Gage A, Mariam DH, Eshetu MK, Arsenault C.",,PLOS global public health,2022,2022-09-12,Y,,,,"The spread of COVID-19 and associated deaths have remained low in Ethiopia. However, the pandemic could pose a public health crisis indirectly through disruptions in essential health services. The aim of this study was to examine disruptions in health service utilization during the first nine months of the COVID-19 pandemic across 10 regions in Ethiopia. We analyzed utilization of 21 different health services across all of Ethiopia (except the Tigray region) for the period of January 2019 to December 2020. Data were extracted from the Ethiopian district health information system (DHIS2). Monthly visits in 2020 were graphed relative to the same months in 2019. Interrupted time series analysis was used to estimate the effect of the pandemic on service utilization in each region. We found that disruptions in health services were generally higher in urban regions which were most affected by COVID. Outpatient visits declined by 52%, 54%, and 58%, specifically in Dire Dawa, Addis Ababa and Harari, the three urban regions. Similarly, there was a 47% reduction in inpatient admissions in Addis Ababa. In agrarian regions, the pandemic caused an 11% to 17% reduction in outpatient visits and a 10% to 27% decline in inpatient admissions. Visits for children with diarrhea, pneumonia and malnutrition also declined substantially while maternal health services were less affected. Our study indicates that disruptions in health services were more pronounced in areas that were relatively harder hit by the pandemic. Our results show that the Ethiopian health system has a limited capacity to absorb shocks. During future waves of COVID or future pandemics, the Ethiopian health system must be better prepared to maintain essential services and mitigate the indirect impact of the pandemic on public health, particularly in urban areas.",,doi:https://doi.org/10.1371/journal.pgph.0000843; html:https://europepmc.org/articles/PMC10021875; pdf:https://europepmc.org/articles/PMC10021875?pdf=render -37127670,https://doi.org/10.1038/s41588-023-01379-x,Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits.,"Zhang BC, Biddanda A, Gunnarsson ÁF, Cooper F, Palamara PF.",,Nature genetics,2023,2023-05-01,Y,,,,"Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N = 134, frequency range 0.0007-0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N = 64). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r = 0.72) underlying sequencing variants enriched (4.8×) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.",,doi:https://doi.org/10.1038/s41588-023-01379-x; html:https://europepmc.org/articles/PMC10181934; pdf:https://europepmc.org/articles/PMC10181934?pdf=render 30862657,https://doi.org/10.2337/dc18-2004,Risk of Incident Obstructive Sleep Apnea Among Patients With Type 2 Diabetes.,"Subramanian A, Adderley NJ, Tracy A, Taverner T, Hanif W, Toulis KA, Thomas GN, Tahrani AA, Nirantharakumar K.",,Diabetes care,2019,2019-03-12,N,,,,"

Objective

This study compared the incidence of obstructive sleep apnea (OSA) in patients with and without type 2 diabetes and investigated risk factors for OSA in patients with type 2 diabetes.

Research design and methods

A retrospective cohort study was performed to compare OSA incidence between adult patients with and without type 2 diabetes matched for age, sex, and BMI. Patients with a prevalent OSA diagnosis were excluded. The study cohort was derived from The Health Improvement Network (THIN), a U.K. primary care database, from 1 January 2005 to 31 December 2017.

Results

There were 3,110 (0.88%) and 5,968 (0.46%) incident OSA cases identified in the 360,250 exposed and 1,296,489 unexposed patient cohorts, respectively. Adjusted incidence rate ratio (aIRR) of OSA in patients with type 2 diabetes compared with those without was 1.48 (95% CI 1.42-1.55; P < 0.001). In a multivariate regression analysis of patients with type 2 diabetes, significant predictors of OSA were diabetes-related foot disease (1.23 [1.06-1.42]; P = 0.005), being prescribed insulin in the last 60 days (1.58 [1.42-1.75]; P < 0.001), male sex (2.27 [2.09-2.46]; P < 0.001), being overweight (2.02 [1.54-2.64]; P < 0.001) or obese (8.29 [6.42-10.69]; P < 0.001), heart failure (1.41 [1.18-1.70]; P < 0.001), ischemic heart disease (1.22 [1.11-1.34]; P < 0.001), atrial fibrillation (1.23 [1.04-1.46]; P = 0.015), hypertension (1.32 [1.23-1.43]; P < 0.001), and depression (1.75 [1.61-1.91]; P < 0.001).

Conclusions

When considered alongside previous evidence, this study indicates that the association between type 2 diabetes and OSA is bidirectional. In addition to known predictors of OSA, diabetes-related foot disease and insulin treatment were identified as risk factors in patients with type 2 diabetes.",,doi:https://doi.org/10.2337/dc18-2004 31650125,https://doi.org/10.1016/s2589-7500(19)30012-3,A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service.,"Kuan V, Denaxas S, Gonzalez-Izquierdo A, Direk K, Bhatti O, Husain S, Sutaria S, Hingorani M, Nitsch D, Parisinos CA, Lumbers RT, Mathur R, Sofat R, Casas JP, Wong ICK, Hemingway H, Hingorani AD.",,The Lancet. Digital health,2019,2019-05-20,Y,,The Human Phenome,,"

Background

To effectively prevent, detect, and treat health conditions that affect people during their lifecourse, health-care professionals and researchers need to know which sections of the population are susceptible to which health conditions and at which ages. Hence, we aimed to map the course of human health by identifying the 50 most common health conditions in each decade of life and estimating the median age at first diagnosis.

Methods

We developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources. Individuals older than 1 year were included in the study if their primary-care and hospital-admission records met research standards set by the Clinical Practice Research Datalink and they had been registered in a general practice in England contributing up-to-standard data for at least 1 year during the study period. We used linked records of individuals from the CALIBER platform to calculate the sex-standardised cumulative incidence for these conditions by 10-year age groups between April 1, 2010, and March 31, 2015. We also derived the median age at diagnosis and prevalence estimates stratified by age, sex, and ethnicity (black, white, south Asian) over the study period from the primary-care and secondary-care records of patients.

Findings

We developed case definitions for 308 disease phenotypes. We used records of 2 784 138 patients for the calculation of cumulative incidence and of 3 872 451 patients for the calculation of period prevalence and median age at diagnosis of these conditions. Conditions that first gained prominence at key stages of life were: atopic conditions and infections that led to hospital admission in children (<10 years); acne and menstrual disorders in the teenage years (10-19 years); mental health conditions, obesity, and migraine in individuals aged 20-29 years; soft-tissue disorders and gastro-oesophageal reflux disease in individuals aged 30-39 years; dyslipidaemia, hypertension, and erectile dysfunction in individuals aged 40-59 years; cancer, osteoarthritis, benign prostatic hyperplasia, cataract, diverticular disease, type 2 diabetes, and deafness in individuals aged 60-79 years; and atrial fibrillation, dementia, acute and chronic kidney disease, heart failure, ischaemic heart disease, anaemia, and osteoporosis in individuals aged 80 years or older. Black or south-Asian individuals were diagnosed earlier than white individuals for 258 (84%) of the 308 conditions. Bone fractures and atopic conditions were recorded earlier in male individuals, whereas female individuals were diagnosed at younger ages with nutritional anaemias, tubulointerstitial nephritis, and urinary disorders.

Interpretation

We have produced the first chronological map of human health with cumulative-incidence and period-prevalence estimates for multiple morbidities in parallel from birth to advanced age. This can guide clinicians, policy makers, and researchers on how to formulate differential diagnoses, allocate resources, and target research priorities on the basis of the knowledge of who gets which diseases when. We have published our phenotyping algorithms on the CALIBER open-access Portal which will facilitate future research by providing a curated list of reusable case definitions.

Funding

Wellcome Trust, National Institute for Health Research, Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Department of Health and Social Care (England), Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Social Care and Health Research, and The Alan Turing Institute.",,doi:https://doi.org/10.1016/S2589-7500(19)30012-3; html:https://europepmc.org/articles/PMC6798263; pdf:https://europepmc.org/articles/PMC6798263?pdf=render +37127670,https://doi.org/10.1038/s41588-023-01379-x,Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits.,"Zhang BC, Biddanda A, Gunnarsson ÁF, Cooper F, Palamara PF.",,Nature genetics,2023,2023-05-01,Y,,,,"Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N = 134, frequency range 0.0007-0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N = 64). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r = 0.72) underlying sequencing variants enriched (4.8×) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.",,doi:https://doi.org/10.1038/s41588-023-01379-x; html:https://europepmc.org/articles/PMC10181934; pdf:https://europepmc.org/articles/PMC10181934?pdf=render 34053260,https://doi.org/10.1098/rstb.2020.0283,Exploring surveillance data biases when estimating the reproduction number: with insights into subpopulation transmission of COVID-19 in England.,"Sherratt K, Abbott S, Meakin SR, Hellewell J, Munday JD, Bosse N, CMMID COVID-19 Working Group, Jit M, Funk S.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Transmission; Surveillance; Bias; Covid-19; Sars-cov-2; Time-varying Reproduction Number,,,"The time-varying reproduction number (Rt: the average number of secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of Rt estimates to different data sources representing COVID-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions and deaths with confirmed COVID-19 in seven regions of England over March through August 2020. We estimated Rt using a model that mapped unobserved infections to each data source. We then compared differences in Rt with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. Rt estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of the disease. We highlight that policy makers could better target interventions by considering the source populations of Rt estimates. Further work should clarify the best way to combine and interpret Rt estimates from different data sources based on the desired use. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0283; html:https://europepmc.org/articles/PMC8165604; pdf:https://europepmc.org/articles/PMC8165604?pdf=render 34563860,https://doi.org/10.1016/j.media.2021.102228,Shape registration with learned deformations for 3D shape reconstruction from sparse and incomplete point clouds.,"Chen X, Ravikumar N, Xia Y, Attar R, Diaz-Pinto A, Piechnik SK, Neubauer S, Petersen SE, Frangi AF.",,Medical image analysis,2021,2021-09-09,N,Deep Learning; Graph Convolutional Network; Cardiac Mesh Reconstruction; Cardiac Surface Reconstruction; Contours To Mesh Reconstruction,,,"Shape reconstruction from sparse point clouds/images is a challenging and relevant task required for a variety of applications in computer vision and medical image analysis (e.g. surgical navigation, cardiac motion analysis, augmented/virtual reality systems). A subset of such methods, viz. 3D shape reconstruction from 2D contours, is especially relevant for computer-aided diagnosis and intervention applications involving meshes derived from multiple 2D image slices, views or projections. We propose a deep learning architecture, coined Mesh Reconstruction Network (MR-Net), which tackles this problem. MR-Net enables accurate 3D mesh reconstruction in real-time despite missing data and with sparse annotations. Using 3D cardiac shape reconstruction from 2D contours defined on short-axis cardiac magnetic resonance image slices as an exemplar, we demonstrate that our approach consistently outperforms state-of-the-art techniques for shape reconstruction from unstructured point clouds. Our approach can reconstruct 3D cardiac meshes to within 2.5-mm point-to-point error, concerning the ground-truth data (the original image spatial resolution is ∼1.8×1.8×10mm3). We further evaluate the robustness of the proposed approach to incomplete data, and contours estimated using an automatic segmentation algorithm. MR-Net is generic and could reconstruct shapes of other organs, making it compelling as a tool for various applications in medical image analysis.",,doi:https://doi.org/10.1016/j.media.2021.102228 33635119,https://doi.org/10.1161/circgen.120.002963,Life-Time Covariation of Major Cardiovascular Diseases: A 40-Year Longitudinal Study and Genetic Studies.,"Lind L, Sundström J, Ärnlöv J, Ingelsson M, Henry A, Lumbers RT, Lampa E.",,Circulation. Genomic and precision medicine,2021,2021-02-26,N,Adult; Myocardial infarction; Atrial fibrillation; Stroke; Heart Failure,,,"

Background

It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs.

Methods

The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used.

Results

Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24-26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4-5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links.

Conclusions

During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.",,doi:https://doi.org/10.1161/CIRCGEN.120.002963; html:https://europepmc.org/articles/PMC8284356; pdf:https://europepmc.org/articles/PMC8284356?pdf=render; doi:https://doi.org/10.1161/circgen.120.002963 @@ -1551,17 +1553,17 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 33637859,https://doi.org/10.1038/s41746-021-00404-9,Automatic multilabel detection of ICD10 codes in Dutch cardiology discharge letters using neural networks.,"Sammani A, Bagheri A, van der Heijden PGM, Te Riele ASJM, Baas AF, Oosters CAJ, Oberski D, Asselbergs FW.",,NPJ digital medicine,2021,2021-02-26,Y,,,,"Standard reference terminology of diagnoses and risk factors is crucial for billing, epidemiological studies, and inter/intranational comparisons of diseases. The International Classification of Disease (ICD) is a standardized and widely used method, but the manual classification is an enormously time-consuming endeavor. Natural language processing together with machine learning allows automated structuring of diagnoses using ICD-10 codes, but the limited performance of machine learning models, the necessity of gigantic datasets, and poor reliability of terminal parts of these codes restricted clinical usability. We aimed to create a high performing pipeline for automated classification of reliable ICD-10 codes in the free medical text in cardiology. We focussed on frequently used and well-defined three- and four-digit ICD-10 codes that still have enough granularity to be clinically relevant such as atrial fibrillation (I48), acute myocardial infarction (I21), or dilated cardiomyopathy (I42.0). Our pipeline uses a deep neural network known as a Bidirectional Gated Recurrent Unit Neural Network and was trained and tested with 5548 discharge letters and validated in 5089 discharge and procedural letters. As in clinical practice discharge letters may be labeled with more than one code, we assessed the single- and multilabel performance of main diagnoses and cardiovascular risk factors. We investigated using both the entire body of text and only the summary paragraph, supplemented by age and sex. Given the privacy-sensitive information included in discharge letters, we added a de-identification step. The performance was high, with F1 scores of 0.76-0.99 for three-character and 0.87-0.98 for four-character ICD-10 codes, and was best when using complete discharge letters. Adding variables age/sex did not affect results. For model interpretability, word coefficients were provided and qualitative assessment of classification was manually performed. Because of its high performance, this pipeline can be useful to decrease the administrative burden of classifying discharge diagnoses and may serve as a scaffold for reimbursement and research applications.",,doi:https://doi.org/10.1038/s41746-021-00404-9; html:https://europepmc.org/articles/PMC7910461; pdf:https://europepmc.org/articles/PMC7910461?pdf=render 34888366,https://doi.org/10.3389/fcvm.2021.768245,MOCOnet: Robust Motion Correction of Cardiovascular Magnetic Resonance T1 Mapping Using Convolutional Neural Networks.,"Gonzales RA, Zhang Q, Papież BW, Werys K, Lukaschuk E, Popescu IA, Burrage MK, Shanmuganathan M, Ferreira VM, Piechnik SK.",,Frontiers in cardiovascular medicine,2021,2021-11-23,Y,image registration; Cardiovascular Magnetic Resonance; T1 Mapping; Deep Learning; Shmolli,,,"Background: Quantitative cardiovascular magnetic resonance (CMR) T1 mapping has shown promise for advanced tissue characterisation in routine clinical practise. However, T1 mapping is prone to motion artefacts, which affects its robustness and clinical interpretation. Current methods for motion correction on T1 mapping are model-driven with no guarantee on generalisability, limiting its widespread use. In contrast, emerging data-driven deep learning approaches have shown good performance in general image registration tasks. We propose MOCOnet, a convolutional neural network solution, for generalisable motion artefact correction in T1 maps. Methods: The network architecture employs U-Net for producing distance vector fields and utilises warping layers to apply deformation to the feature maps in a coarse-to-fine manner. Using the UK Biobank imaging dataset scanned at 1.5T, MOCOnet was trained on 1,536 mid-ventricular T1 maps (acquired using the ShMOLLI method) with motion artefacts, generated by a customised deformation procedure, and tested on a different set of 200 samples with a diverse range of motion. MOCOnet was compared to a well-validated baseline multi-modal image registration method. Motion reduction was visually assessed by 3 human experts, with motion scores ranging from 0% (strictly no motion) to 100% (very severe motion). Results: MOCOnet achieved fast image registration (<1 second per T1 map) and successfully suppressed a wide range of motion artefacts. MOCOnet significantly reduced motion scores from 37.1±21.5 to 13.3±10.5 (p < 0.001), whereas the baseline method reduced it to 15.8±15.6 (p < 0.001). MOCOnet was significantly better than the baseline method in suppressing motion artefacts and more consistently (p = 0.007). Conclusion: MOCOnet demonstrated significantly better motion correction performance compared to a traditional image registration approach. Salvaging data affected by motion with robustness and in a time-efficient manner may enable better image quality and reliable images for immediate clinical interpretation.",,doi:https://doi.org/10.3389/fcvm.2021.768245; html:https://europepmc.org/articles/PMC8649951; pdf:https://europepmc.org/articles/PMC8649951?pdf=render 31055854,https://doi.org/10.5694/mja2.50143,"Traumatic spinal cord injury in Victoria, 2007-2016.","Beck B, Cameron PA, Braaf S, Nunn A, Fitzgerald MC, Judson RT, Teague WJ, Lennox A, Middleton JW, Harrison JE, Gabbe BJ.",,The Medical journal of Australia,2019,2019-05-01,N,"Spinal cord injuries; epidemiology; Traumatology; Trauma, Nervous System",,,"

Objective

To investigate trends in the incidence and causes of traumatic spinal cord injury (TSCI) in Victoria over a 10-year period.

Design, setting, participants

Retrospective cohort study: analysis of Victorian State Trauma Registry (VSTR) data for people who sustained TSCIs during 2007-2016.

Main outcomes and measures

Temporal trends in population-based incidence rates of TSCI (injury to the spinal cord with an Abbreviated Injury Scale [AIS] score of 4 or more).

Results

There were 706 cases of TSCI, most the result of transport events (269 cases, 38%) or low falls (197 cases, 28%). The overall crude incidence of TSCI was 1.26 cases per 100 000 population (95% CI, 1.17-1.36 per 100 000 population), and did not change over the study period (incidence rate ratio [IRR], 1.01; 95% CI, 0.99-1.04). However, the incidence of TSCI resulting from low falls increased by 9% per year (95% CI, 4-15%). The proportion of TSCI cases classified as incomplete tetraplegia increased from 41% in 2007 to 55% in 2016 (P < 0.001). Overall in-hospital mortality was 15% (104 deaths), and was highest among people aged 65 years or more (31%, 70 deaths).

Conclusions

Given the devastating consequences of TSCI, improved primary prevention strategies are needed, particularly as the incidence of TSCI did not decline over the study period. The epidemiologic profile of TSCI has shifted, with an increasing number of TSCI events in older adults. This change has implications for prevention, acute and post-discharge care, and support.",,doi:https://doi.org/10.5694/mja2.50143 -31145509,https://doi.org/10.1002/gepi.22215,A comparison of two workflows for regulome and transcriptome-based prioritization of genetic variants associated with myocardial mass.,"Manduchi E, Hemerich D, van Setten J, Tragante V, Harakalova M, Pei J, Williams SM, van der Harst P, Asselbergs FW, Moore JH.",,Genetic epidemiology,2019,2019-05-30,N,Functional genomics; Gwas; left ventricular mass; Snp Preselection,,,"A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine-map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.",,doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215 33323251,https://doi.org/10.1016/s2589-7500(19)30123-2,A comparison of deep learning performance against health-care professionals in detecting diseases from medical imaging: a systematic review and meta-analysis.,"Liu X, Faes L, Kale AU, Wagner SK, Fu DJ, Bruynseels A, Mahendiran T, Moraes G, Shamdas M, Kern C, Ledsam JR, Schmid MK, Balaskas K, Topol EJ, Bachmann LM, Keane PA, Denniston AK.",,The Lancet. Digital health,2019,2019-09-25,N,,,,"

Background

Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases using medical imaging.

Methods

In this systematic review and meta-analysis, we searched Ovid-MEDLINE, Embase, Science Citation Index, and Conference Proceedings Citation Index for studies published from Jan 1, 2012, to June 6, 2019. Studies comparing the diagnostic performance of deep learning models and health-care professionals based on medical imaging, for any disease, were included. We excluded studies that used medical waveform data graphics material or investigated the accuracy of image segmentation rather than disease classification. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. Studies undertaking an out-of-sample external validation were included in a meta-analysis, using a unified hierarchical model. This study is registered with PROSPERO, CRD42018091176.

Findings

Our search identified 31 587 studies, of which 82 (describing 147 patient cohorts) were included. 69 studies provided enough data to construct contingency tables, enabling calculation of test accuracy, with sensitivity ranging from 9·7% to 100·0% (mean 79·1%, SD 0·2) and specificity ranging from 38·9% to 100·0% (mean 88·3%, SD 0·1). An out-of-sample external validation was done in 25 studies, of which 14 made the comparison between deep learning models and health-care professionals in the same sample. Comparison of the performance between health-care professionals in these 14 studies, when restricting the analysis to the contingency table for each study reporting the highest accuracy, found a pooled sensitivity of 87·0% (95% CI 83·0-90·2) for deep learning models and 86·4% (79·9-91·0) for health-care professionals, and a pooled specificity of 92·5% (95% CI 85·1-96·4) for deep learning models and 90·5% (80·6-95·7) for health-care professionals.

Interpretation

Our review found the diagnostic performance of deep learning models to be equivalent to that of health-care professionals. However, a major finding of the review is that few studies presented externally validated results or compared the performance of deep learning models and health-care professionals using the same sample. Additionally, poor reporting is prevalent in deep learning studies, which limits reliable interpretation of the reported diagnostic accuracy. New reporting standards that address specific challenges of deep learning could improve future studies, enabling greater confidence in the results of future evaluations of this promising technology.

Funding

None.",,doi:https://doi.org/10.1016/S2589-7500(19)30123-2; pdf:http://www.thelancet.com/article/S2589750019301232/pdf +31145509,https://doi.org/10.1002/gepi.22215,A comparison of two workflows for regulome and transcriptome-based prioritization of genetic variants associated with myocardial mass.,"Manduchi E, Hemerich D, van Setten J, Tragante V, Harakalova M, Pei J, Williams SM, van der Harst P, Asselbergs FW, Moore JH.",,Genetic epidemiology,2019,2019-05-30,N,Functional genomics; Gwas; left ventricular mass; Snp Preselection,,,"A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine-map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.",,doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215 31702773,https://doi.org/10.1093/bioinformatics/btz796,Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.,"Orlenko A, Kofink D, Lyytikäinen LP, Nikus K, Mishra P, Kuukasjärvi P, Karhunen PJ, Kähönen M, Laurikka JO, Lehtimäki T, Asselbergs FW, Moore JH.",,"Bioinformatics (Oxford, England)",2020,2020-03-01,Y,,,,"

Motivation

Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES).

Results

We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes.

Availability and implementation

TPOT is freely available via http://epistasislab.github.io/tpot/.

Supplementary information

Supplementary data are available at Bioinformatics online.",,doi:https://doi.org/10.1093/bioinformatics/btz796; html:https://europepmc.org/articles/PMC7703753; pdf:https://europepmc.org/articles/PMC7703753?pdf=render 34459239,https://doi.org/10.1161/jaha.120.021115,Factor V Leiden and the Risk of Bleeding in Patients With Acute Coronary Syndromes Treated With Antiplatelet Therapy: Pooled Analysis of 3 Randomized Clinical Trials.,"Mahmoodi BK, Eriksson N, Ross S, Claassens DMF, Asselbergs FW, Meijer K, Siegbahn A, James S, Pare G, Wallentin L, Ten Berg JM.",,Journal of the American Heart Association,2021,2021-08-28,Y,Bleeding; acute coronary syndrome; Factor V Leiden; Antiplatelet Therapy,,,"Background Whether factor V Leiden is associated with lower bleeding risk in patients with acute coronary syndromes using (dual) antiplatelet therapy has yet to be investigated. Methods and Results We pooled data from 3 randomized clinical trials, conducted in patients with acute coronary syndromes, with adjudicated bleeding outcomes. Cox regression models were used to obtain overall and cause-specific hazard ratios (HRs) to account for competing risk of atherothrombotic outcomes (ie, composite of ischemic stroke, myocardial infarction, and cardiovascular death) in each study. Estimates from the individual studies were pooled using fixed effect meta-analysis. The 3 studies combined included 17 623 patients of whom 969 (5.5%) were either heterozygous or homozygous (n=23) carriers of factor V Leiden. During 1 year of follow-up, a total of 1289 (7.3%) patients developed major (n=559) or minor bleeding. Factor V Leiden was associated with a lower risk of combined major and minor bleeding (adjusted cause-specific HR, 0.75; 95% CI, 0.56-1.00; P=0.046; I2=0%) but a comparable risk of major bleeding (adjusted cause-specific HR, 0.93; 95% CI, 0.62-1.39; P=0.73; I2=0%). Adjusted pooled cause-specific HRs for the association of factor V Leiden with atherothrombotic events alone and in combination with bleeding events were 0.75 (95% CI, 0.55-1.02; P=0.06; I2=0%) and 0.75 (95% CI, 0.61-0.92; P=0.007; I2=0%), respectively. Conclusions Given that the lower risk of bleeding conferred by factor V Leiden was not counterbalanced by a higher risk of atherothrombotic events, these findings warrant future assessment for personalized medicine such as selecting patients for extended or intensive antiplatelet therapy.",,doi:https://doi.org/10.1161/JAHA.120.021115; html:https://europepmc.org/articles/PMC8649290; pdf:https://europepmc.org/articles/PMC8649290?pdf=render 33090454,https://doi.org/10.1111/bjd.19597,Atopic eczema and obesity: a population-based study.,"Ascott A, Mansfield KE, Schonmann Y, Mulick A, Abuabara K, Roberts A, Smeeth L, Langan SM.",,The British journal of dermatology,2021,2020-12-01,N,,,,"

Background

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.

Objectives

To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index.

Methods

We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without.

Results

We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema.

Conclusions

We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.",,doi:https://doi.org/10.1111/bjd.19597 -35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render 33246414,https://doi.org/10.1186/s12874-020-01163-z,Patient-specific record linkage between emergency department and hospital admission data for a cohort of people who inject drugs: methodological considerations for frequent presenters.,"Di Rico R, Nambiar D, Gabbe B, Stoové M, Dietze P.",,BMC medical research methodology,2020,2020-11-27,Y,Methods; Australia; Data Linkage; Record Linkage; Administrative Data; People Who Inject Drugs; Patient Pathways; Frequent Presenters; Vaed; Vemd,,,"

Background

People who inject drugs (PWID) have been identified as frequent users of emergency department (ED) and hospital inpatient services. The specific challenges of record linkage in cohorts with numerous administrative health records occurring in close proximity are not well understood. Here, we present a method for patient-specific record linkage of ED and hospital admission data for a cohort of PWID.

Methods

Data from 688 PWID were linked to two state-wide administrative health databases identifying all ED visits and hospital admissions for the cohort between January 2008 and June 2013. We linked patient-specific ED and hospital admissions data, using administrative date-time timestamps and pre-specified linkage criteria, to identify hospital admissions stemming from ED presentations for a given individual. The ability of standalone databases to identify linked ED visits or hospital admissions was examined.

Results

There were 3459 ED visits and 1877 hospital admissions identified during the study period. Thirty-four percent of ED visits were linked to hospital admissions. Most links had hospital admission timestamps in-between or identical to their ED visit timestamps (n = 1035, 87%). Allowing 24-h between ED visits and hospital admissions captured more linked records, but increased manual inspection requirements. In linked records (n = 1190), the ED 'departure status' variable correctly reflected subsequent hospital admission in only 68% of cases. The hospital 'admission type' variable was non-specific in identifying if a preceding ED visit had occurred.

Conclusions

Linking ED visits with subsequent hospital admissions in PWID requires access to date and time variables for accurate temporal sorting, especially for same-day presentations. Selecting time-windows to capture linked records requires discretion. Researchers risk under-ascertainment of hospital admissions if using ED data alone.",,doi:https://doi.org/10.1186/s12874-020-01163-z; html:https://europepmc.org/articles/PMC7694355; pdf:https://europepmc.org/articles/PMC7694355?pdf=render +35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render 37269091,https://doi.org/10.1177/10870547231172763,Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.,"Sun S, Denyer H, Sankesara H, Deng Q, Ranjan Y, Conde P, Rashid Z, Bendayan R, Asherson P, Bilbow A, Groom M, Hollis C, Folarin AA, Dobson RJB, Kuntsi J.",,Journal of attention disorders,2023,2023-06-02,Y,ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base,,,"

Objective

We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system.

Method

We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40).

Results

The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes.

Conclusion

Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",,doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render -35247983,https://doi.org/10.1186/s12877-021-02673-1,"Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.","Henkens MTHM, Raafs AG, Verdonschot JAJ, Linschoten M, van Smeden M, Wang P, van der Hooft BHM, Tieleman R, Janssen MLF, Ter Bekke RMA, Hazebroek MR, van der Horst ICC, Asselbergs FW, Magdelijns FJH, Heymans SRB, CAPACITY-COVID collaborative consortium.",,BMC geriatrics,2022,2022-03-05,Y,Mortality; Hospitalization; Netherlands; Mediation Analysis; Covid-19,,,"

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).",,doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render -37433797,https://doi.org/10.1038/s41467-023-38816-8,The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom.,"Brand SPC, Cavallaro M, Cumming F, Turner C, Florence I, Blomquist P, Hilton J, Guzman-Rincon LM, House T, Nokes DJ, Keeling MJ.",,Nature communications,2023,2023-07-11,Y,,,,"Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.",,doi:https://doi.org/10.1038/s41467-023-38816-8; html:https://europepmc.org/articles/PMC10336136; pdf:https://europepmc.org/articles/PMC10336136?pdf=render +35247983,https://doi.org/10.1186/s12877-021-02673-1,"Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.","Henkens MTHM, Raafs AG, Verdonschot JAJ, Linschoten M, van Smeden M, Wang P, van der Hooft BHM, Tieleman R, Janssen MLF, Ter Bekke RMA, Hazebroek MR, van der Horst ICC, Asselbergs FW, Magdelijns FJH, Heymans SRB, CAPACITY-COVID collaborative consortium.",,BMC geriatrics,2022,2022-03-05,Y,Mortality; Hospitalization; Netherlands; Mediation Analysis; Covid-19,,,"

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).",,doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render; doi:https://doi.org/10.1186/s12877-021-02673-1 32294163,https://doi.org/10.1093/europace/euaa039,Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation.,"Bosman LP, Cadrin-Tourigny J, Bourfiss M, Aliyari Ghasabeh M, Sharma A, Tichnell C, Roudijk RW, Murray B, Tandri H, Khairy P, Kamel IR, Zimmerman SL, Reitsma JB, Asselbergs FW, van Tintelen JP, van der Heijden JF, Hauer RNW, Calkins H, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2020,2020-05-01,Y,Diagnosis; Cardiomyopathy; ventricular arrhythmia; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation.

Methods and results

We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%).

Conclusion

The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.",,doi:https://doi.org/10.1093/europace/euaa039; html:https://europepmc.org/articles/PMC7203633; pdf:https://europepmc.org/articles/PMC7203633?pdf=render +37433797,https://doi.org/10.1038/s41467-023-38816-8,The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom.,"Brand SPC, Cavallaro M, Cumming F, Turner C, Florence I, Blomquist P, Hilton J, Guzman-Rincon LM, House T, Nokes DJ, Keeling MJ.",,Nature communications,2023,2023-07-11,Y,,,,"Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.",,doi:https://doi.org/10.1038/s41467-023-38816-8; html:https://europepmc.org/articles/PMC10336136; pdf:https://europepmc.org/articles/PMC10336136?pdf=render 33947203,https://doi.org/10.1161/circulationaha.120.053033,Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.,"Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, Celeghin R, Edwards M, Fan J, Ingles J, James CA, Jarinova O, Johnson R, Judge DP, Lahrouchi N, Lekanne Deprez RH, Lumbers RT, Mazzarotto F, Medeiros Domingo A, Miller RL, Morales A, Murray B, Peters S, Pilichou K, Protonotarios A, Semsarian C, Shah P, Syrris P, Thaxton C, van Tintelen JP, Walsh R, Wang J, Ware J, Hershberger RE.",,Circulation,2021,2021-05-05,Y,Genetics; Cardiomyopathy,,,"

Background

Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.

Methods

An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated.

Results

Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%; ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence.

Conclusions

In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.",,doi:https://doi.org/10.1161/CIRCULATIONAHA.120.053033; html:https://europepmc.org/articles/PMC8247549; pdf:https://europepmc.org/articles/PMC8247549?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.053033 35354069,https://doi.org/10.1016/j.cmet.2022.03.002,Early prediction of incident liver disease using conventional risk factors and gut-microbiome-augmented gradient boosting.,"Liu Y, Méric G, Havulinna AS, Teo SM, Åberg F, Ruuskanen M, Sanders J, Zhu Q, Tripathi A, Verspoor K, Cheng S, Jain M, Jousilahti P, Vázquez-Baeza Y, Loomba R, Lahti L, Niiranen T, Salomaa V, Knight R, Inouye M.",,Cell metabolism,2022,2022-03-29,Y,Prediction; Gut; Disease; Microbiota; liver disease; Metagenomics; Microbiome,,,"The gut microbiome has shown promise as a predictive biomarker for various diseases. However, the potential of gut microbiota for prospective risk prediction of liver disease has not been assessed. Here, we utilized shallow shotgun metagenomic sequencing of a large population-based cohort (N > 7,000) with ∼15 years of follow-up in combination with machine learning to investigate the predictive capacity of gut microbial predictors individually and in conjunction with conventional risk factors for incident liver disease. Separately, conventional and microbial factors showed comparable predictive capacity. However, microbiome augmentation of conventional risk factors using machine learning significantly improved the performance. Similarly, disease-free survival analysis showed significantly improved stratification using microbiome-augmented models. Investigation of predictive microbial signatures revealed previously unknown taxa for liver disease, as well as those previously associated with hepatic function and disease. This study supports the potential clinical validity of gut metagenomic sequencing to complement conventional risk factors for prediction of liver diseases.",,doi:https://doi.org/10.1016/j.cmet.2022.03.002; html:https://europepmc.org/articles/PMC9097589 34863512,https://doi.org/10.1016/j.bja.2021.10.038,Review of the requirements for effective mass casualty preparedness for trauma systems. A disaster waiting to happen?,"Gabbe BJ, Veitch W, Mather A, Curtis K, Holland AJA, Gomez D, Civil I, Nathens A, Fitzgerald M, Martin K, Teague WJ, Joseph A.",,British journal of anaesthesia,2022,2021-12-02,N,Disaster Preparedness; Mass Casualty Incidents; Trauma Systems; Narrative Review; Trauma Centres,,,"Mass casualty incidents (MCIs) are diverse, unpredictable, and increasing in frequency, but preparation is possible and necessary. The nature of MCIs requires a trauma response but also requires effective and tested disaster preparedness planning. From an international perspective, the aims of this narrative review are to describe the key components necessary for optimisation of trauma system preparedness for MCIs, whether trauma systems and centres meet these components and areas for improvement of trauma system response. Many of the principles necessary for response to MCIs are embedded in trauma system design and trauma centre function. These include robust communication networks, established triage systems, and capacity to secure centres from threats to safety and quality of care. However, evidence from the current literature indicates the need to strengthen trauma system preparedness for MCIs through greater trauma leader representation at all levels of disaster preparedness planning, enhanced training of staff and simulated disaster training, expanded surge capacity planning, improved staff management and support during the MCI and in the post-disaster recovery phase, clear provision for the treatment of paediatric patients in disaster plans, and diversified and pre-agreed systems for essential supplies and services continuity. Mass casualty preparedness is a complex, iterative process that requires an integrated, multidisciplinary, and tiered approach. Through effective preparedness planning, trauma systems should be well-placed to deliver an optimal response when faced with MCIs.",,doi:https://doi.org/10.1016/j.bja.2021.10.038 @@ -1574,7 +1576,7 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 32075790,https://doi.org/10.1136/bmj.m331,Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study.,"Fan H, Gilbert R, O'Callaghan F, Li L.",,BMJ (Clinical research ed.),2020,2020-02-19,Y,,,,"

Objective

To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children.

Design

Population based cohort study.

Setting

The UK Clinical Practice Research Datalink.

Participants

The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort.

Main outcome measures

Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder.

Results

Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses.

Conclusions

Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available.

Trial registration

ClinicalTrials.gov NCT03948620.",,doi:https://doi.org/10.1136/bmj.m331; html:https://europepmc.org/articles/PMC7190043 34965929,https://doi.org/10.1136/bmj-2021-065834,GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.,"Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.",,BMJ (Clinical research ed.),2021,2021-12-29,Y,,,,"

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.",,doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render 34470746,https://doi.org/10.1136/bmjgh-2021-006204,Disruption in essential health services in Mexico during COVID-19: an interrupted time series analysis of health information system data.,"Doubova SV, Leslie HH, Kruk ME, Pérez-Cuevas R, Arsenault C.",,BMJ global health,2021,2021-09-01,Y,Hypertension; Cancer; Diabetes; Maternal Health; Health Systems Evaluation,,,"

Introduction

The COVID-19 pandemic has disrupted health systems around the world. The objectives of this study are to estimate the overall effect of the pandemic on essential health service use and outcomes in Mexico, describe observed and predicted trends in services over 24 months, and to estimate the number of visits lost through December 2020.

Methods

We used health information system data for January 2019 to December 2020 from the Mexican Institute of Social Security (IMSS), which provides health services for more than half of Mexico's population-65 million people. Our analysis includes nine indicators of service use and three outcome indicators for reproductive, maternal and child health and non-communicable disease services. We used an interrupted time series design and linear generalised estimating equation models to estimate the change in service use and outcomes from April to December 2020. Estimates were expressed using average marginal effects on the risk ratio scale.

Results

The study found that across nine health services, an estimated 8.74 million patient visits were lost in Mexico. This included a decline of over two thirds for breast and cervical cancer screenings (79% and 68%, respectively), over half for sick child visits and female contraceptive services, approximately one-third for childhood vaccinations, diabetes, hypertension and antenatal care consultations, and a decline of 10% for deliveries performed at IMSS. In terms of patient outcomes, the proportion of patients with diabetes and hypertension with controlled conditions declined by 22% and 17%, respectively. Caesarean section rate did not change.

Conclusion

Significant disruptions in health services show that the pandemic has strained the resilience of the Mexican health system and calls for urgent efforts to resume essential services and plan for catching up on missed preventive care even as the COVID-19 crisis continues in Mexico.",,doi:https://doi.org/10.1136/bmjgh-2021-006204; html:https://europepmc.org/articles/PMC8413469; pdf:https://europepmc.org/articles/PMC8413469?pdf=render -34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render +34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render; pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf 31492797,https://doi.org/10.1136/bmjopen-2019-032165,Evaluation of the impact of the GRACE risk score on the management and outcome of patients hospitalised with non-ST elevation acute coronary syndrome in the UK: protocol of the UKGRIS cluster-randomised registry-based trial.,"Everett CC, Fox KA, Reynolds C, Fernandez C, Sharples L, Stocken DD, Carruthers K, Hemingway H, Yan AT, Goodman SG, Brieger D, Chew DP, Gale CP.",,BMJ open,2019,2019-09-05,Y,Risk stratification; acute coronary syndrome; Grace; Nsteacs; Cluster Randomised Trial; Guideline-indicated Treatment,"Better, Faster and More Efficient Clinical Trials",,"INTRODUCTION:For non-ST-segment elevation acute coronary syndrome (NSTEACS) there is a gap between the use of class I guideline recommended therapies and clinical practice. The Global Registry of Acute Coronary Events (GRACE) risk score is recommended in international guidelines for the risk stratification of NSTEACS, but its impact on adherence to guideline-indicated treatments and reducing adverse clinical outcomes is unknown. The objective of the UK GRACE Risk Score Intervention Study (UKGRIS) trial is to assess the effectiveness of the GRACE risk score tool and associated treatment recommendations on the use of guideline-indicated care and clinical outcomes. METHODS AND ANALYSIS:The UKGRIS, a parallel-group cluster randomised registry-based controlled trial, will allocate hospitals in a 1:1 ratio to manage NSTEACS by standard care or according to the GRACE risk score and associated international guidelines. UKGRIS will recruit a minimum of 3000 patients from at least 30 English National Health Service hospitals and collect healthcare data from national electronic health records. The co-primary endpoints are the use of guideline-indicated therapies, and the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospitalisation or cardiovascular readmission at 12 months. Secondary endpoints include duration of inpatient hospital stay over 12 months, EQ-5D-5L responses and utilities, unscheduled revascularisation and the components of the composite endpoint over 12 months follow-up. ETHICS AND DISSEMINATION:The study has ethical approval (North East - Tyne & Wear South Research Ethics Committee reference: 14/NE/1180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder's open access policy. TRIAL REGISTRATION NUMBER:ISRCTN29731761; Pre-results.",,doi:https://doi.org/10.1136/bmjopen-2019-032165; html:https://europepmc.org/articles/PMC6731819; pdf:https://europepmc.org/articles/PMC6731819?pdf=render 32222069,https://doi.org/10.1111/bjd.19052,Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.,"Yiu ZZN, Parisi R, Lunt M, Warren RB, Griffiths CEM, Langan SM, Ashcroft DM.",,The British journal of dermatology,2021,2020-05-12,N,,,,"

Background

Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear.

Objectives

To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection.

Methods

We conducted a cohort study of people (≥ 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection.

Results

There were 69 315 people with psoriasis and 338 620 comparators who were followed up for a median (interquartile range) of 4·9 (5·9) and 5·1 (6·3) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20·5 per 1000 person-years, 95% confidence interval (CI) 20·0-21·0, n = 7631] compared with those without psoriasis (16·1 per 1000 person-years, 95% CI 15·9-16·3, n = 30 761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1·36 (95% CI 1·31-1·40), with similar results across the other outcomes.

Conclusions

Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.",,doi:https://doi.org/10.1111/bjd.19052 35834561,https://doi.org/10.1371/journal.pmed.1004039,"Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.","Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE.",,PLoS medicine,2022,2022-07-14,Y,,,,"

Background

Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits.

Methods and findings

Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 ± 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the ""Snap"" card game. Mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (β = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (β = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy.

Conclusions

To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.",,doi:https://doi.org/10.1371/journal.pmed.1004039; html:https://europepmc.org/articles/PMC9282660; pdf:https://europepmc.org/articles/PMC9282660?pdf=render @@ -1597,18 +1599,18 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 35388009,https://doi.org/10.1038/s41467-022-29641-6,Publisher Correction: Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.,"Stacey D, Chen L, Stanczyk PJ, Howson JMM, Mason AM, Burgess S, MacDonald S, Langdown J, McKinney H, Downes K, Farahi N, Peters JE, Basu S, Pankow JS, Tang W, Pankratz N, Sabater-Lleal M, de Vries PS, Smith NL, CHARGE Hemostasis Working Group, Gelinas AD, Schneider DJ, Janjic N, Samani NJ, Ye S, Summers C, Chilvers ER, Danesh J, Paul DS.",,Nature communications,2022,2022-04-06,Y,,,,,,doi:https://doi.org/10.1038/s41467-022-29641-6; html:https://europepmc.org/articles/PMC8986867; pdf:https://europepmc.org/articles/PMC8986867?pdf=render 35068290,https://doi.org/10.1080/09537104.2021.2003317,Higher body mass index raises immature platelet count: potential contribution to obesity-related thrombosis.,"Goudswaard LJ, Corbin LJ, Burley KL, Mumford A, Akbari P, Soranzo N, Butterworth AS, Watkins NA, Pournaras DJ, Harris J, Timpson NJ, Hers I.",,Platelets,2022,2022-01-24,N,Obesity; Aggregation; epidemiology; Mendelian Randomization; Immature Platelets,,,"Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.",,doi:https://doi.org/10.1080/09537104.2021.2003317 35421974,https://doi.org/10.1186/s12911-022-01842-5,An implementation framework and a feasibility evaluation of a clinical decision support system for diabetes management in secondary mental healthcare using CogStack.,"Patel D, Msosa YJ, Wang T, Mustafa OG, Gee S, Williams J, Roberts A, Dobson RJ, Gaughran F.",,BMC medical informatics and decision making,2022,2022-04-14,Y,Monitoring; Diabetes; Clinical Decision Support; Pre-diabetes; Ehealth; Alerting; Cogstack,,,"

Background

Improvements to the primary prevention of physical health illnesses like diabetes in the general population have not been mirrored to the same extent in people with serious mental illness (SMI). This work evaluates the technical feasibility of implementing an electronic clinical decision support system (eCDSS) for supporting the management of dysglycaemia and diabetes in patients with serious mental illness in a secondary mental healthcare setting.

Methods

A stepwise approach was taken as an overarching and guiding framework for this work. Participatory methods were employed to design and deploy a monitoring and alerting eCDSS. The eCDSS was evaluated for its technical feasibility. The initial part of the feasibility evaluation was conducted in an outpatient community mental health team. Thereafter, the evaluation of the eCDSS progressed to a more in-depth in silico validation.

Results

A digital health intervention that enables monitoring and alerting of at-risk patients based on an approved diabetes management guideline was developed. The eCDSS generated alerts according to expected standards and in line with clinical guideline recommendations.

Conclusions

It is feasible to design and deploy a functional monitoring and alerting eCDSS in secondary mental healthcare. Further work is required in order to fully evaluate the integration of the eCDSS into routine clinical workflows. By describing and sharing the steps that were and will be taken from concept to clinical testing, useful insights could be provided to teams that are interested in building similar digital health interventions.",,doi:https://doi.org/10.1186/s12911-022-01842-5; html:https://europepmc.org/articles/PMC9009062; pdf:https://europepmc.org/articles/PMC9009062?pdf=render -37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render 31699727,https://doi.org/10.1136/bmjopen-2019-030882,Optical coherence tomography (OCT) in unconscious and systemically unwell patients using a mobile OCT device: a pilot study.,"Liu X, Kale AU, Capewell N, Talbot N, Ahmed S, Keane PA, Mollan S, Belli A, Blanch RJ, Veenith T, Denniston AK.",,BMJ open,2019,2019-11-07,Y,optical coherence tomography; Optical Coherence Tomography Angiography; Adult Intensive & Critical Care,,,"

Objective

This study aims to evaluate the feasibility of retinal imaging in critical care using a novel mobile optical coherence tomography (OCT) device. The Heidelberg SPECTRALIS FLEX module (Heidelberg Engineering, Heidelberg, Germany) is an OCT unit with a boom arm, enabling ocular OCT assessment in less mobile patients.

Design

We undertook an evaluation of the feasibility of using the SPECTRALIS FLEX for undertaking ocular OCT images in unconscious and critically ill patients.

Setting

This study was conducted in the critical care unit of a large tertiary referral unit in the United Kingdom.

Participants

13 systemically unwell patients admitted to the critical care unit were purposively sampled to enable evaluation in patients with a range of clinical states.

Outcome measures

The primary outcome was the feasibility of acquiring clinically interpretable OCT scans on a consecutive series of patients. The standardised scanning protocol included macula-focused OCT, OCT optic nerve head (ONH), OCT angiography (OCTA) of the macula and ONH OCTA.

Results

OCT images from 13 patients were attempted. The success rates of each scan type are 84% for OCT macula, 76% for OCT ONH, 56% for OCTA macula and 36% for OCTA ONH. The overall mean success rate of scans per patient was 64% (95% CI 46% to 81%). Clinicians reported clinical value in 100% scans which were successfully obtained, including both ruling in and ruling out relevant ocular complications such as corneal thinning, macular oedema and optic disc swelling. The most common causes of failure to achieve clinically interpretable scans were inadequately sustained OCT alignment in delirious patients and a compromised ocular surface due to corneal exposure.

Conclusions

This prospective evaluation indicates the feasibility and potential clinical value of the SPECTRALIS FLEX OCT system on the critical care unit. Portable OCT systems have the potential to bring instrument-based ophthalmic assessment to critically ill patients, enabling detection and micron-level monitoring of ocular complications.",,doi:https://doi.org/10.1136/bmjopen-2019-030882; html:https://europepmc.org/articles/PMC6858135; pdf:https://europepmc.org/articles/PMC6858135?pdf=render +37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable 35094586,https://doi.org/10.1177/17407745221077691,The PROTEUS-Trials Consortium: Optimizing the use of patient-reported outcomes in clinical trials.,"Snyder C, Crossnohere N, King M, Reeve BB, Bottomley A, Calvert M, Thorner E, Wu AW, Brundage M, PROTEUS-Trials Consortium.",,"Clinical trials (London, England)",2022,2022-01-31,Y,Clinical Trials; Protocols; Data Visualization; Patient-reported Outcomes; Reporting Methods; Measure Selection,,,"

Background

The assessment of patient-reported outcomes in clinical trials has enormous potential to promote patient-centred care, but for this potential to be realized, the patient-reported outcomes must be captured effectively and communicated clearly. Over the past decade, methodologic tools have been developed to inform the design, analysis, reporting, and interpretation of patient-reported outcome data from clinical trials. We formed the PROTEUS-Trials Consortium (Patient-Reported Outcomes Tools: Engaging Users and Stakeholders) to disseminate and implement these methodologic tools.

Methods

PROTEUS-Trials are engaging with patient, clinician, research, and regulatory stakeholders from 27 organizations in the United States, Canada, Australia, the United Kingdom, and Europe to develop both organization-specific and cross-cutting strategies for implementing and disseminating the methodologic tools. Guided by the Knowledge-to-Action framework, we conducted consortium-wide webinars and meetings, as well as individual calls with participating organizations, to develop a workplan, which we are currently executing.

Results

Six methodologic tools serve as the foundation for PROTEUS-Trials dissemination and implementation efforts: the Standard Protocol Items: Recommendations for Interventional Trials-patient-reported outcome extension for writing protocols with patient-reported outcomes, the International Society for Quality of Life Research Minimum Standards for selecting a patient-reported outcome measure, Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium recommendations for patient-reported outcome data analysis, the Consolidated Standards for Reporting of Trials-patient-reported outcome extension for reporting clinical trials with patient-reported outcomes, recommendations for the graphic display of patient-reported outcome data, and a Clinician's Checklist for reading and using an article about patient-reported outcomes. The PROTEUS-Trials website (www.TheProteusConsortium.org) serves as a central repository for the methodologic tools and associated resources. To date, we have developed (1) a roadmap to visually display where each of the six methodologic tools applies along the clinical trial trajectory, (2) web tutorials that provide guidance on the methodologic tools at different levels of detail, (3) checklists to provide brief summaries of each tool's recommendations, (4) a handbook to provide a self-guided approach to learning about the tools and recommendations, and (5) publications that address key topics related to patient-reported outcomes in clinical trials. We are also conducting organization-specific activities, including meetings, presentations, workshops, and webinars to publicize the existence of the methodologic tools and the PROTEUS-Trials resources. Work to develop communications strategies to ensure that PROTEUS-Trials reach key audiences with relevant information about patient-reported outcomes in clinical trials and PROTEUS-Trials is ongoing.

Discussion

The PROTEUS-Trials Consortium aims to help researchers generate patient-reported outcome data from clinical trials to (1) enable investigators, regulators, and policy-makers to take the patient perspective into account when conducting research and making decisions; (2) help patients understand treatment options and make treatment decisions; and (3) inform clinicians' discussions with patients regarding treatment options. In these ways, the PROTEUS Consortium promotes patient-centred research and care.",,doi:https://doi.org/10.1177/17407745221077691; html:https://europepmc.org/articles/PMC9203669; pdf:https://europepmc.org/articles/PMC9203669?pdf=render 32040531,https://doi.org/10.1371/journal.pone.0228940,Risk assessment for hospital admission in patients with COPD; a multi-centre UK prospective observational study.,"Fermont JM, Bolton CE, Fisk M, Mohan D, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Wilkinson IB, Wood AM, Polkey MI, Müllerova H.",,PloS one,2020,2020-02-10,Y,,Better Care,,"In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs. The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand). We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay. Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD. Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales. The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES). In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up. Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD. For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD). The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD. The SPPB can aid in clinical decision making and when prioritising healthcare resources.","This article looks at risk assessment for hospital admission in patients with Chronic Obstructive Pulmonary Disease (COPD), which is a group of lung conditions that make it difficult to empty air out of the lungs. The objective of the risk assessment was to eventually aid in clinical decision making and prioritising healthcare resources.",doi:https://doi.org/10.1371/journal.pone.0228940; html:https://europepmc.org/articles/PMC7010290; pdf:https://europepmc.org/articles/PMC7010290?pdf=render -36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276; doi:https://doi.org/10.1016/s2214-109x(23)00007-4 33888728,https://doi.org/10.1038/s41598-021-86331-x,A multidimensional measure of polypharmacy for older adults using the Health and Retirement Study.,"Carr E, Federman A, Dzahini O, Dobson RJ, Bendayan R.",,Scientific reports,2021,2021-04-22,Y,,,,"Polypharmacy is commonly defined based on the number of medications taken concurrently using standard cut-offs, but several studies have highlighted the need for a multidimensional assessment. We developed a multidimensional measure of polypharmacy and compared with standard cut-offs. Data were extracted for 2141 respondents of the 2007 Prescription Drug Survey, a sub-study of the Health Retirement Study. Latent classes were identified based on multiple indicators of polypharmacy, including quantity, temporality and risk profile. A four-class model was selected based on fit statistics and clinical interpretability: 'High risk, long-term' (Class 1), 'Low risk, long-term' (Class 2), 'High risk, short-term' (Class 3), and 'High risk for drug interactions, medium-term, regular' (Class 4). Classes differed regarding sex, cohabitation, disability and multimorbidity. Participants in the 'low risk' class tended to be male, cohabitating, and reported fewer health conditions, compared to 'high risk' classes. Polypharmacy classes were compared to standard cut-offs (5+ or 9+ medications) in terms of overlap and mortality risk. The three 'high risk' classes overlapped with the groups concurrently taking 5+ and 9+ medications per month. However, the multidimensional measure further differentiated individuals in terms of risk profile and temporality of medication taking, thus offering a richer assessment of polypharmacy.",,doi:https://doi.org/10.1038/s41598-021-86331-x; html:https://europepmc.org/articles/PMC8062687; pdf:https://europepmc.org/articles/PMC8062687?pdf=render +36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276; doi:https://doi.org/10.1016/s2214-109x(23)00007-4 34767555,https://doi.org/10.1371/journal.pmed.1003832,Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.,"Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.",,PLoS medicine,2021,2021-11-12,Y,,,,"

Background

Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.

Methods and findings

Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.

Conclusions

Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.",,doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render 35000827,https://doi.org/10.1016/j.clon.2021.12.017,Can Real-world Data and Rapid Learning Drive Improvements in Lung Cancer Survival? The RAPID-RT Study.,"Price G, Devaney S, French DP, Holley R, Holm S, Kontopantelis E, McWilliam A, Payne K, Proudlove N, Sanders C, Willans R, van Staa T, Hamrang L, Turner B, Parsons S, Faivre-Finn C.",,Clinical oncology (Royal College of Radiologists (Great Britain)),2022,2022-01-06,N,,,,,,doi:https://doi.org/10.1016/j.clon.2021.12.017 -36401199,https://doi.org/10.1186/s12888-022-04275-6,Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.,"Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, Hübel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.",,BMC psychiatry,2022,2022-11-18,Y,Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping,,,"

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.",,doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render 37118290,https://doi.org/10.1038/s43587-022-00293-x,Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases.,"Lindbohm JV, Mars N, Sipilä PN, Singh-Manoux A, Runz H, FinnGen, Livingston G, Seshadri S, Xavier R, Hingorani AD, Ripatti S, Kivimäki M.",,Nature aging,2022,2022-10-14,Y,,,,"Immune system and blood-brain barrier dysfunction are implicated in the development of Alzheimer's and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood-brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer's disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49-0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases.",,doi:https://doi.org/10.1038/s43587-022-00293-x; html:https://europepmc.org/articles/PMC10154235; pdf:https://europepmc.org/articles/PMC10154235?pdf=render; pdf:https://www.nature.com/articles/s43587-022-00293-x.pdf -33025017,https://doi.org/10.1093/schbul/sbaa126,Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,"Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.",,Schizophrenia bulletin,2021,2021-03-01,N,Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing,,,"

Background

Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.

Method

The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.

Results

A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.

Conclusions

Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.",,doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf +36401199,https://doi.org/10.1186/s12888-022-04275-6,Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.,"Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, Hübel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.",,BMC psychiatry,2022,2022-11-18,Y,Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping,,,"

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.",,doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render 30082368,https://doi.org/10.1136/bmjopen-2018-024755,Validating injury burden estimates using population birth cohorts and longitudinal cohort studies of injury outcomes: the VIBES-Junior study protocol.,"Gabbe BJ, Dipnall JF, Lynch JW, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Simpson PM, Beck B, Demmler JC, Lyons J, Schneeberg A, Harrison JE.",,BMJ open,2018,2018-08-05,Y,epidemiology; Public Health; Paediatrics; Trauma Management,"Improving Public Health, The Human Phenome",,"

Introduction

Traumatic injury is a leading contributor to the global disease burden in children and adolescents, but methods used to estimate burden do not account for differences in patterns of injury and recovery between children and adults. A lack of empirical data on postinjury disability in children has limited capacity to derive valid disability weights and describe the long-term individual and societal impacts of injury in the early part of life. The aim of this study is to establish valid estimates of the burden of non-fatal injury in children and adolescents.

Methods and analysis

Five longitudinal studies of paediatric injury survivors <18 years at the time of injury (Australia, Canada, UK and USA) and two whole-of-population linked administrative data paediatric studies (Australia and Wales) will be analysed over a 3-year period commencing 2018. Meta-analysis of deidentified patient-level data (n≈2,600) from five injury-specific longitudinal studies (Victorian State Trauma Registry; Victorian Orthopaedic Trauma Outcomes Registry; UK Burden of Injury; British Columbia Children's Hospital Longitudinal Injury Outcomes; Children's Health After Injury) and >1 million children from two whole-of-population cohorts (South Australian Early Childhood Data Project and Wales Electronic Cohort for Children). Systematic analysis of pooled injury-specific cohort data using a variety of statistical techniques, and parallel analysis of whole-of-population cohorts, will be used to develop estimated disability weights for years lost due to disability, establish appropriate injury classifications and explore factors influencing recovery.

Ethics and dissemination

The project was approved by the Monash University Human Research Ethics Committee project number 12 311. Results of this study will be submitted for publication in internationally peer-reviewed journals. The findings from this project have the capacity to improve the validity of paediatric injury burden measurements in future local and global burden of disease studies.",,doi:https://doi.org/10.1136/bmjopen-2018-024755; html:https://europepmc.org/articles/PMC6078268; pdf:https://europepmc.org/articles/PMC6078268?pdf=render +33025017,https://doi.org/10.1093/schbul/sbaa126,Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,"Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.",,Schizophrenia bulletin,2021,2021-03-01,N,Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing,,,"

Background

Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.

Method

The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.

Results

A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.

Conclusions

Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.",,doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf 31820220,https://doi.org/10.1007/s10926-019-09867-w,The Association Between Fault Attribution and Work Participation After Road Traffic Injury: A Registry-Based Observational Study.,"Lau G, Gabbe BJ, Collie A, Ponsford J, Ameratunga S, Cameron PA, Harrison JE, Giummarra MJ.",,Journal of occupational rehabilitation,2020,2020-06-01,N,Trauma; Injury; Recovery; Traffic; Accidents; Return To Work,,,"Purpose To characterise associations between fault attribution and work participation and capacity after road traffic injury. Methods People aged 15-65 years, working pre-injury, without serious brain injury, who survived to 12 months after road traffic injury were included from two Victorian trauma registries (n = 2942). Fault profiles from linked compensation claims were defined as no other at fault, another at fault, denied another at fault, claimed another at fault, and unknown. Claimant reports in the denied and claimed another at fault groups contradicted police reports. Patients reported work capacity (Glasgow outcome scale-extended) and return to work (RTW) at 6, 12 and 24 months post-injury (early and sustained RTW, delayed RTW (≥ 12 months), failed RTW attempts, no RTW attempts). Analyses adjusted for demographic, clinical and injury covariates. Results The risk of not returning to work was higher if another was at fault [adjusted relative risk ratio (aRRR) = 1.67, 95% confidence interval (CI) 1.29, 2.17] or was claimed to be at fault (aRRR = 1.58, 95% CI 1.04, 2.41), and lower for those who denied that another was at fault (aRRR = 0.51, 95% CI 0.29, 0.91), compared to cases with no other at fault. Similarly, people had higher odds of work capacity limitations if another was at fault (12m: AOR = 1.49, 95% CI 1.24, 1.80; 24m: 1.63, 95% CI 1.35, 1.97) or was claimed to be at fault (12m: AOR = 1.54, 95% CI 1.16, 2.05; 24m: AOR = 1.80, 95% CI 1.34, 2.41), and lower odds if they denied another was at fault (6m: AOR = 0.67, 95% CI 0.48, 0.95), compared to cases with no other at fault. Conclusion Targeted interventions are needed to support work participation in people at risk of poor RTW post-injury. While interventions targeting fault and justice-related attributions are currently lacking, these may be beneficial for people who believe that another caused their injury.",,doi:https://doi.org/10.1007/s10926-019-09867-w 35507331,https://doi.org/10.1002/art.42154,Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling.,"Soomro M, Stadler M, Dand N, Bluett J, Jadon D, Jalali-Najafabadi F, Duckworth M, Ho P, Marzo-Ortega H, Helliwell PS, Ryan AW, Kane D, Korendowych E, Simpson MA, Packham J, McManus R, Gabay C, Lamacchia C, Nissen MJ, Brown MA, Verstappen SMM, Van Staa T, Barker JN, Smith CH, BADBIR Study Group, BSTOP study group, FitzGerald O, McHugh N, Warren RB, Bowes J, Barton A.",,"Arthritis & rheumatology (Hoboken, N.J.)",2022,2022-08-04,Y,,,,"

Objectives

Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.

Methods

Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.

Results

We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP  = 0.63), which was similar to the heritability of PsC (h2 SNP  = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.

Conclusion

Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.",,doi:https://doi.org/10.1002/art.42154; html:https://europepmc.org/articles/PMC9539852; pdf:https://europepmc.org/articles/PMC9539852?pdf=render 32542387,https://doi.org/10.1093/jac/dkaa222,Towards personalized guidelines: using machine-learning algorithms to guide antimicrobial selection.,"Moran E, Robinson E, Green C, Keeling M, Collyer B.",,The Journal of antimicrobial chemotherapy,2020,2020-09-01,N,,,,"

Background

Electronic decision support systems could reduce the use of inappropriate or ineffective empirical antibiotics. We assessed the accuracy of an open-source machine-learning algorithm trained in predicting antibiotic resistance for three Gram-negative bacterial species isolated from patients' blood and urine within 48 h of hospital admission.

Methods

This retrospective, observational study used routine clinical information collected between January 2010 and October 2016 in Birmingham, UK. Patients from whose blood or urine cultures Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa was isolated were identified. Their demographic, microbiology and prescribing data were used to train an open-source machine-learning algorithm-XGBoost-in predicting resistance to co-amoxiclav and piperacillin/tazobactam. Multivariate analysis was performed to identify predictors of resistance and create a point-scoring tool. The performance of both methods was compared with that of the original prescribers.

Results

There were 15 695 admissions. The AUC of the receiver operating characteristic curve for the point-scoring tools ranged from 0.61 to 0.67, and performed no better than medical staff in the selection of appropriate antibiotics. The machine-learning system performed statistically but marginally better (AUC 0.70) and could have reduced the use of unnecessary broad-spectrum antibiotics by as much as 40% among those given co-amoxiclav, piperacillin/tazobactam or carbapenems. A validation study is required.

Conclusions

Machine-learning algorithms have the potential to help clinicians predict antimicrobial resistance in patients found to have a Gram-negative infection of blood or urine. Prospective studies are required to assess performance in an unselected patient cohort, understand the acceptability of such systems to clinicians and patients, and assess the impact on patient outcome.",,doi:https://doi.org/10.1093/jac/dkaa222; html:https://europepmc.org/articles/PMC7443728; pdf:https://europepmc.org/articles/PMC7443728?pdf=render; doi:https://doi.org/10.1093/jac/dkaa222 @@ -1619,20 +1621,20 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34593247,https://doi.org/10.1016/j.injury.2021.09.027,An evaluation of the association between fault attribution and healthcare costs and trajectories in the first three years after transport injury.,"Melita J G, Joanna F D, Alex C, Jennie P, Shanthi A, Belinda J G.",,Injury,2021,2021-09-20,N,Trauma; Compensation; Insurance; Biopsychosocial; Health Service Use,,,"

Background

People with complex medical and psychosocial issues have high healthcare needs. This registry-based cohort study sought to quantify the association between external fault attribution, recorded during compensation claim lodgement, and the cost and patterns of healthcare utilisation.

Methods

6,144 survivors of transport-related major trauma between 1 July 2010 and 30 June 2016 were extracted from the Victorian State Trauma Registry (VSTR) and linked to treatment payments from the Transport Accident Commission (TAC). Associations between fault and healthcare costs were examined with Generalised Linear Regression. Healthcare trajectories were identified using Group-Based Multi-Trajectory Modelling and included medical treatments from a physician, or pain, mental health and physical therapy treatments for the first three years post-injury. Trajectories were validated against the EQ-5D-3L health status summary score using mixed linear regression.

Results

While injury severity had the strongest association with healthcare use, people who attributed fault to another had 9% higher healthcare costs. Six multi-trajectory groups were identified: 36% had low treatments over time; 25% had a rapid decline from high medical and physical therapy by 12-months; 12% had moderate to high medical and physical therapy that declined by 2-3 years; 11% had a gradual decline in medical treatment, an early increase in physical therapy but low pain and mental health treatment; 8% had high or increasing medical and physical therapy, moderate mental health therapy and low pain treatment; and 7% had moderate-high treatment across all domains. All groups had poorer health status compared with the group with low treatment levels, and people who attributed fault to another had higher risk of following trajectories with higher levels of treatment versus the low treatment group (beta=0.34, SE=0.12, p=0.01).

Conclusion

These findings highlight the need to provide pro-active multidisciplinary care coordination for people with complex needs after injury to better optimise recovery.",,doi:https://doi.org/10.1016/j.injury.2021.09.027 32811694,https://doi.org/10.1016/j.burns.2020.01.005,Driving improved burns care and patient outcomes through clinical registry data: A review of quality indicators in the Burns Registry of Australia and New Zealand.,"Gong J, Singer Y, Cleland H, Wood F, Cameron P, Tracy LM, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2021,2020-08-15,N,Burns; Quality Indicators; Clinical Quality Registry,,,"

Background

In 2009, the Burns Registry of Australia and New Zealand (BRANZ) published a set of clinical quality indicators (QIs) to monitor performance, improve quality of care, and inform and change policy. With several years of data collected since the initial development of the indicators for burns, the BRANZ QI Working Party reviewed the clinical QIs for relevance and meaning, and considered new QIs that had not been collected previously.

Method

Using published literature and expert opinion, the QI Working Party, consisting of multidisciplinary burn clinicians, reviewed the QIs for burn care to be included as routine data items in the BRANZ.

Results

In July 2016, the list of clinical QIs in the BRANZ was updated to 23 QIs/data items, covering structure, process, and outcome measures. Four QIs were removed as they were not found to be useful, nine QIs/data items were revised, and eight new QIs/data items were added as they were considered to be clinically useful.

Conclusion

This review outlines the changes made to the QIs collected by the BRANZ four years since their development and implementation. Ongoing refinement of the BRANZ QIs will ensure that high quality data is collected to drive improvements in clinical and patient outcomes.",,doi:https://doi.org/10.1016/j.burns.2020.01.005 35331425,https://doi.org/10.1016/j.jacep.2021.09.001,Clinical Characteristics and Follow-Up of Pediatric-Onset Arrhythmogenic Right Ventricular Cardiomyopathy.,"Roudijk RW, Verheul L, Bosman LP, Bourfiss M, Breur JMPJ, Slieker MG, Blank AC, Dooijes D, van der Heijden JF, van den Heuvel F, Clur SA, Udink Ten Cate FEA, van den Berg MP, Wilde AAM, Asselbergs FW, Peter van Tintelen J, Te Riele ASJM.",,JACC. Clinical electrophysiology,2022,2021-12-22,N,Genetics; Ventricular tachycardia; Heart Failure; Sudden Cardiac Death; Arrhythmogenic Right Ventricular Cardiomyopathy; Pediatric-onset; Cascade Screening,,,"

Objectives

The goal of this study was to describe characteristics, cascade screening results, and predictors of adverse outcome in pediatric-onset arrhythmogenic right ventricular cardiomyopathy (ARVC).

Background

Although ARVC is increasingly recognized in children, pediatric ARVC cohorts remain underrepresented in the literature.

Methods

This study included 12 probands with pediatric-onset ARVC (aged <18 years at diagnosis) and 68 pediatric relatives (aged <18 years at first evaluation) referred for cascade screening. ARVC diagnosis was based on 2010 Task Force Criteria. Clinical presentation, diagnostic testing, and outcomes (sustained ventricular tachycardia [VT]; heart failure) were ascertained. Predictors of adverse outcome were determined by using univariable logistic regression.

Results

Pediatric-onset ARVC was diagnosed in 12 probands and 12 (18%) relatives at a median age of 16.6 years (interquartile range: 13.8-17.4 years), whereas 12 (18%) relatives reached ARVC diagnosis as adults (median age, 22.0 years; interquartile range: 20.0-26.7 years). Sudden cardiac death/arrest was the first disease manifestation in 3 (25%) probands and 3 (4%) relatives. In patients without ARVC diagnosis at presentation (n = 61), electrocardiogram and Holter monitoring abnormalities occurred before development of imaging Task Force Criteria (7.3 ± 5.0 years vs 8.4 ± 5.0 years). Clinical course was characterized by sustained VT (91%) and heart failure (36%) in probands, which were rare in relatives (2% and 0%, respectively). Male sex (P < 0.01), T-wave inversion V1-V3 (P < 0.01), premature ventricular complexes/runs (P ≤ 0.01), and decrease in biventricular ejection fraction (P ≤ 0.01) were associated with VT occurrence.

Conclusions

Pediatric ARVC carries high arrhythmic risk, especially in probands. Disease progression is particularly observed on electrocardiogram or Holter monitoring. Arrhythmic events are associated with male sex, T-wave inversions, premature ventricular complexes/runs, and reduced biventricular ejection fraction.",,doi:https://doi.org/10.1016/j.jacep.2021.09.001 -34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render 31815634,https://doi.org/10.1186/s12933-019-0972-4,Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study.,"Bromage DI, Godec TR, Pujades-Rodriguez M, Gonzalez-Izquierdo A, Denaxas S, Hemingway H, Yellon DM.",,Cardiovascular diabetology,2019,2019-12-09,Y,Acute myocardial infarction; Type 2 diabetes; Cohort studies; Metformin; cardioprotection; Outcomes,,,"

Background

The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England.

Methods

This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality.

Results

4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1-1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01-1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62-0.93], P = 0.009).

Conclusions

Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.",,doi:https://doi.org/10.1186/s12933-019-0972-4; html:https://europepmc.org/articles/PMC6900858; pdf:https://europepmc.org/articles/PMC6900858?pdf=render +34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render 33185016,https://doi.org/10.1002/art.41593,Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.,"Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-05-01,Y,,,,"

Objective

To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.

Methods

We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.

Results

During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.

Conclusion

No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.",,doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render 35710247,https://doi.org/10.1136/bmjopen-2021-060280,Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.,"Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.",,BMJ open,2022,2022-06-16,Y,Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders,,,"

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.",,doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render +31233103,https://doi.org/10.1093/bioinformatics/btz469,PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.,"Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, Butterworth AS, Staley JR.",,"Bioinformatics (Oxford, England)",2019,2019-11-01,Y,,Applied Analytics,,"

Summary

PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants.

Availability and implementation

PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.",Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.,doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render 36719157,https://doi.org/10.2215/cjn.05080422,Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: A Mendelian Randomization Study.,"Donovan K, Herrington WG, Paré G, Pigeyre M, Haynes R, Sardell R, Butterworth AS, Folkersen L, Gustafsson S, Wang Q, Baigent C, Mälarstig A, Holmes MV, Staplin N, on behalf of the SCALLOP Consortium .",,Clinical journal of the American Society of Nephrology : CJASN,2023,2023-01-01,Y,,,,"

Background

Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.

Methods

SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).

Results

We identified 34 independent variants for circulating FGF-23, which formed a validated genetic score. There were no associations between genetically predicted FGF-23 and any of the cardiovascular or noncardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities.

Conclusions

Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link.

Podcast

This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3.",,doi:https://doi.org/10.2215/CJN.05080422; html:https://europepmc.org/articles/PMC7614195; pdf:https://europepmc.org/articles/PMC7614195?pdf=render; pdf:http://uu.diva-portal.org/smash/get/diva2:1745425/FULLTEXT01 -31233103,https://doi.org/10.1093/bioinformatics/btz469,PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.,"Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, Butterworth AS, Staley JR.",,"Bioinformatics (Oxford, England)",2019,2019-11-01,Y,,Applied Analytics,,"

Summary

PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants.

Availability and implementation

PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.",Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.,doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render 33062309,https://doi.org/10.1177/2059513120952336,Epidemiology of burn injury in older adults: An Australian and New Zealand perspective.,"Tracy LM, Singer Y, Schrale R, Gong J, Darton A, Wood F, Kurmis R, Edgar D, Cleland H, Gabbe BJ.",,"Scars, burns & healing",2020,2020-01-01,Y,Burns; Australia; New Zealand; Older Adults; scald; Burn Database,,,"

Introduction

The ageing global population presents a novel set of challenges for trauma systems. Less research has focused on the older adult population with burns and how they differ compared to younger patients. This study aimed to describe, and compare with younger peers, the number, causes and surgical management of older adults with burn injuries in Australia and New Zealand.

Methods

The Burns Registry of Australia and New Zealand was used to identify patients with burn injuries between 1 July 2009 and 31 December 2018. Temporal trends in incidence rates were evaluated and categorised by age at injury. Patient demographics, injury severity and event characteristics, surgical intervention and in-hospital outcomes were investigated.

Results

There were 2394 burn-injured older adults admitted during the study period, accounting for 13.4% of adult admissions. Scalds were the most common cause of burn injury in older adults. The incidence of older adult burns increased by 2.96% each year (incidence rate ratio = 1.030, 95% confidence interval = 1.013-1.046, P < 0.001). Compared to their younger peers, a smaller proportion of older adult patients were taken to theatre for a surgical procedure, though a larger proportion of older adults received a skin graft.

Discussion

Differences in patient and injury characteristics, surgical management and in-hospital outcomes were observed for older adults. These findings provide the Australian and New Zealand burn care community with a greater understanding of burn injury and their treatments in a unique group of patients who are at risk of poorer outcomes than younger people.

Lay summary

The number and proportion of older persons in every country of the world is growing. This may create challenges for healthcare systems. While burn injuries are a unique subset of trauma that affect individuals of all ages, less is known about burns in older adults and how they differ from younger patients.We wanted to look at the number, type, management, and outcomes of burns in older adults in Australia and New Zealand. To do this, we used data from the Burns Registry of Australia and New Zealand, or BRANZ. The BRANZ is a database that collects information on patients that present to Australian and New Zealand hospitals that have a specialist burns unit.Our research found that one in eight adult burns patients was over the age of 65, and that the rate of burn injuries in older adults has increased over the last decade. Older adult burns patients were most commonly affected by scalds after coming in contact with wet heat such as boiling liquids or steam. Fewer older adults went to theatre for an operation or surgical procedure compared to their younger counterparts. However, a larger proportion of older adults that went to theatre had a skin graft (where skin is removed from an uninjured part of the body and placed over the injured part).This research provides important information about a unique and growing group of patients to the local burn care community. It also highlights potential avenues for injury prevention initiatives.",,doi:https://doi.org/10.1177/2059513120952336; html:https://europepmc.org/articles/PMC7534068; pdf:https://europepmc.org/articles/PMC7534068?pdf=render 33905882,https://doi.org/10.1016/j.media.2021.102050,Phenotype discovery from population brain imaging.,"Gong W, Beckmann CF, Smith SM.",,Medical image analysis,2021,2021-03-31,Y,Neuroimaging; Uk Biobank; Behaviour Prediction; Phenotype Discovery; Multimodal Independent Component Analysis,,,"Neuroimaging allows for the non-invasive study of the brain in rich detail. Data-driven discovery of patterns of population variability in the brain has the potential to be extremely valuable for early disease diagnosis and understanding the brain. The resulting patterns can be used as imaging-derived phenotypes (IDPs), and may complement existing expert-curated IDPs. However, population datasets, comprising many different structural and functional imaging modalities from thousands of subjects, provide a computational challenge not previously addressed. Here, for the first time, a multimodal independent component analysis approach is presented that is scalable for data fusion of voxel-level neuroimaging data in the full UK Biobank (UKB) dataset, that will soon reach 100,000 imaged subjects. This new computational approach can estimate modes of population variability that enhance the ability to predict thousands of phenotypic and behavioural variables using data from UKB and the Human Connectome Project. A high-dimensional decomposition achieved improved predictive power compared with widely-used analysis strategies, single-modality decompositions and existing IDPs. In UKB data (14,503 subjects with 47 different data modalities), many interpretable associations with non-imaging phenotypes were identified, including multimodal spatial maps related to fluid intelligence, handedness and disease, in some cases where IDP-based approaches failed.",,doi:https://doi.org/10.1016/j.media.2021.102050; html:https://europepmc.org/articles/PMC8850869; pdf:https://europepmc.org/articles/PMC8850869?pdf=render -34310590,https://doi.org/10.1371/journal.pcbi.1009098,Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era.,"Prem K, Zandvoort KV, Klepac P, Eggo RM, Davies NG, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Cook AR, Jit M.",,PLoS computational biology,2021,2021-07-26,Y,,,,"Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.",,doi:https://doi.org/10.1371/journal.pcbi.1009098; html:https://europepmc.org/articles/PMC8354454; pdf:https://europepmc.org/articles/PMC8354454?pdf=render 33325834,https://doi.org/10.2196/23530,Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.,"Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.",,JMIR medical informatics,2020,2020-12-16,Y,Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface,,,"

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.",,doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511 -33769566,https://doi.org/10.1111/bph.15459,Emerging therapies and their delivery for treating age-related macular degeneration.,"Thomas CN, Sim DA, Lee WH, Alfahad N, Dick AD, Denniston AK, Hill LJ.",,British journal of pharmacology,2022,2021-05-12,N,Retina; Complement; Immunotherapy; Age-related macular degeneration; Drug Delivery; Anti-vegf; Ocular Disease,,,"Age-related macular degeneration (AMD) is the most common cause of blindness in the Western world and is characterised in its latter stages by retinal cell death and neovascularisation and earlier stages with the loss of parainflammatory homeostasis. Patients with neovascular AMD (nAMD) are treated with frequent intraocular injections of anti-vascular endothelial growth factor (VEGF) therapies, which are not only unpopular with patients but carry risks of sight-threatening complications. A minority of patients are unresponsive with no alternative treatment available, and some patients who respond initially eventually develop a tolerance to treatment. New therapeutics with improved delivery methods and sustainability of clinical effects are required, in particular for non-neovascular AMD (90% of cases and no current approved treatments). There are age-related and disease-related changes that occur which can affect ocular drug delivery. Here, we review the latest emerging therapies for AMD, their delivery routes and implications for translating to clinical practice. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.",,doi:https://doi.org/10.1111/bph.15459 +34310590,https://doi.org/10.1371/journal.pcbi.1009098,Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era.,"Prem K, Zandvoort KV, Klepac P, Eggo RM, Davies NG, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Cook AR, Jit M.",,PLoS computational biology,2021,2021-07-26,Y,,,,"Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.",,doi:https://doi.org/10.1371/journal.pcbi.1009098; html:https://europepmc.org/articles/PMC8354454; pdf:https://europepmc.org/articles/PMC8354454?pdf=render 32845538,https://doi.org/10.1634/theoncologist.2020-0572,Cancer and Risk of COVID-19 Through a General Community Survey.,"Lee KA, Ma W, Sikavi DR, Drew DA, Nguyen LH, Bowyer RCE, Cardoso MJ, Fall T, Freidin MB, Gomez M, Graham M, Guo CG, Joshi AD, Kwon S, Lo CH, Lochlainn MN, Menni C, Murray B, Mehta R, Song M, Sudre CH, Bataille V, Varsavsky T, Visconti A, Franks PW, Wolf J, Steves CJ, Ourselin S, Spector TD, Chan AT, COPE consortium.",,The oncologist,2021,2020-09-07,Y,,,,"Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.",,doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render +33769566,https://doi.org/10.1111/bph.15459,Emerging therapies and their delivery for treating age-related macular degeneration.,"Thomas CN, Sim DA, Lee WH, Alfahad N, Dick AD, Denniston AK, Hill LJ.",,British journal of pharmacology,2022,2021-05-12,N,Retina; Complement; Immunotherapy; Age-related macular degeneration; Drug Delivery; Anti-vegf; Ocular Disease,,,"Age-related macular degeneration (AMD) is the most common cause of blindness in the Western world and is characterised in its latter stages by retinal cell death and neovascularisation and earlier stages with the loss of parainflammatory homeostasis. Patients with neovascular AMD (nAMD) are treated with frequent intraocular injections of anti-vascular endothelial growth factor (VEGF) therapies, which are not only unpopular with patients but carry risks of sight-threatening complications. A minority of patients are unresponsive with no alternative treatment available, and some patients who respond initially eventually develop a tolerance to treatment. New therapeutics with improved delivery methods and sustainability of clinical effects are required, in particular for non-neovascular AMD (90% of cases and no current approved treatments). There are age-related and disease-related changes that occur which can affect ocular drug delivery. Here, we review the latest emerging therapies for AMD, their delivery routes and implications for translating to clinical practice. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.",,doi:https://doi.org/10.1111/bph.15459 33692554,https://doi.org/10.1038/s41586-021-03243-6,Improving reporting standards for polygenic scores in risk prediction studies.,"Wand H, Lambert SA, Tamburro C, Iacocca MA, O'Sullivan JW, Sillari C, Kullo IJ, Rowley R, Dron JS, Brockman D, Venner E, McCarthy MI, Antoniou AC, Easton DF, Hegele RA, Khera AV, Chatterjee N, Kooperberg C, Edwards K, Vlessis K, Kinnear K, Danesh JN, Parkinson H, Ramos EM, Roberts MC, Ormond KE, Khoury MJ, Janssens ACJW, Goddard KAB, Kraft P, MacArthur JAL, Inouye M, Wojcik GL.",,Nature,2021,2021-03-10,N,,,,"Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.",,doi:https://doi.org/10.1038/s41586-021-03243-6; html:https://europepmc.org/articles/PMC8609771; pdf:https://europepmc.org/articles/PMC8609771?pdf=render; doi:https://doi.org/10.1038/s41586-021-03243-6 35505938,https://doi.org/10.1016/j.eclinm.2022.101417,Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.,"Hampshire A, Chatfield DA, MPhil AM, Jolly A, Trender W, Hellyer PJ, Giovane MD, Newcombe VFJ, Outtrim JG, Warne B, Bhatti J, Pointon L, Elmer A, Sithole N, Bradley J, Kingston N, Sawcer SJ, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, and Cambridge NIHR Clinical Research Facility.",,EClinicalMedicine,2022,2022-04-28,Y,Memory; Cognition; Attention; Planning; Cognitive Assessment; Reasoning; Covid-19,,,"

Background

Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.

Methods

46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (N = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using N = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.

Findings

COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (p=​​0.0037) and G_RT (p = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.

Interpretation

Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.

Funding

This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.",,doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render 34091032,https://doi.org/10.1016/j.neuroimage.2021.118235,Subspace-constrained approaches to low-rank fMRI acceleration.,"Mason HT, Graedel NN, Miller KL, Chiew M.",,NeuroImage,2021,2021-06-03,Y,fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors,,,"Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.",,doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render @@ -1657,8 +1659,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34547359,https://doi.org/10.1016/j.jaad.2021.09.018,Mixed evidence on the relationship between socioeconomic position and atopic dermatitis: A systematic review.,"Bajwa H, Baghchechi M, Mujahid M, Kang Dufour MS, Langan SM, Abuabara K.",,Journal of the American Academy of Dermatology,2022,2021-09-20,N,dermatitis; Socioeconomic status; Eczema; Atopic; Socioeconomic Position,,,"

Background

Lower socioeconomic position usually portends worse health outcomes, but multiple studies have found that atopic dermatitis is associated with higher socioeconomic position. The nature of this relationship remains unclear.

Objective

To systematically review the literature on socioeconomic position and atopic dermatitis and determine whether the association varies by patient or study characteristics.

Methods

A literature search was conducted in the PubMed and Embase databases. Individual-level studies addressing the association between all measures of socioeconomic position and the prevalence or incidence of atopic dermatitis were eligible for inclusion. Two independent reviewers screened all texts and extracted all data for qualitative synthesis.

Results

Eighty-eight studies met the inclusion criteria. Of the 88 studies, 42% (37) found a positive association between atopic dermatitis and socioeconomic position, 15% (13) found a negative association, and 43% (38) found a null or inconsistent association. Studies conducted in Europe, among children, and based on self-report of eczema were more likely to find a positive association with socioeconomic position.

Limitations

Studies varied both in terms of the measurement of socioeconomic position and the definition of atopic dermatitis, limiting quantitative synthesis.

Conclusion

The evidence of a positive association between atopic dermatitis and socioeconomic position is not consistent.",,doi:https://doi.org/10.1016/j.jaad.2021.09.018; html:https://europepmc.org/articles/PMC8810617; pdf:https://europepmc.org/articles/PMC8810617?pdf=render; doi:https://doi.org/10.1016/j.jaad.2021.09.018 34568585,https://doi.org/10.23889/ijpds.v6i1.1671,Linking education and hospital data in England: linkage process and quality.,"Libuy N, Harron K, Gilbert R, Caulton R, Cameron E, Blackburn R.",,International journal of population data science,2021,2021-09-16,Y,Bias; Data Linkage; Record Linkage; Administrative Data; Hospital Records; Linkage Error; Educational Records,,,"

Introduction

Linkage of administrative data for universal state education and National Health Service (NHS) hospital care would enable research into the inter-relationships between education and health for all children in England.

Objectives

We aim to describe the linkage process and evaluate the quality of linkage of four one-year birth cohorts within the National Pupil Database (NPD) and Hospital Episode Statistics (HES).

Methods

We used multi-step deterministic linkage algorithms to link longitudinal records from state schools to the chronology of records in the NHS Personal Demographics Service (PDS; linkage stage 1), and HES (linkage stage 2). We calculated linkage rates and compared pupil characteristics in linked and unlinked samples for each stage of linkage and each cohort (1990/91, 1996/97, 1999/00, and 2004/05).

Results

Of the 2,287,671 pupil records, 2,174,601 (95%) linked to HES. Linkage rates improved over time (92% in 1990/91 to 99% in 2004/05). Ethnic minority pupils and those living in more deprived areas were less likely to be matched to hospital records, but differences in pupil characteristics between linked and unlinked samples were moderate to small.

Conclusion

We linked nearly all pupils to at least one hospital record. The high coverage of the linkage represents a unique opportunity for wide-scale analyses across the domains of health and education. However, missed links disproportionately affected ethnic minorities or those living in the poorest neighbourhoods: selection bias could be mitigated by increasing the quality and completeness of identifiers recorded in administrative data or the application of statistical methods that account for missed links.

Highlights

Longitudinal administrative records for all children attending state school and acute hospital services in England have been used for research for more than two decades, but lack of a shared unique identifier has limited scope for linkage between these databases.We applied multi-step deterministic linkage algorithms to 4 one-year cohorts of children born 1 September-31 August in 1990/91, 1996/97, 1999/00 and 2004/05. In stage 1, full names, date of birth, and postcode histories from education data in the National Pupil Database were linked to the NHS Personal Demographic Service. In stage 2, NHS number, postcode, date of birth and sex were linked to hospital records in Hospital Episode Statistics.Between 92% and 99% of school pupils linked to at least one hospital record. Ethnic minority pupils and pupils who were living in the most deprived areas were least likely to link. Ethnic minority pupils were less likely than white children to link at the first step in both algorithms.Bias due to linkage errors could lead to an underestimate of the health needs in disadvantaged groups. Improved data quality, more sensitive linkage algorithms, and/or statistical methods that account for missed links in analyses, should be considered to reduce linkage bias.",,doi:https://doi.org/10.23889/ijpds.v6i1.1671; html:https://europepmc.org/articles/PMC8445153; pdf:https://europepmc.org/articles/PMC8445153?pdf=render 34139154,https://doi.org/10.1016/j.cels.2021.05.005,A time-resolved proteomic and prognostic map of COVID-19.,"Demichev V, Tober-Lau P, Lemke O, Nazarenko T, Thibeault C, Whitwell H, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Aulakh SK, Helbig ET, Stubbemann P, Lippert LJ, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Ralser M, Kurth F.",,Cell systems,2021,2021-06-14,Y,Proteomics; Biomarkers; Physiological parameters; Machine Learning; Disease Prognosis; Clinical Disease Progression; Patient Trajectories; Longitudinal Profiling; Covid-19,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.",,doi:https://doi.org/10.1016/j.cels.2021.05.005; html:https://europepmc.org/articles/PMC8201874; doi:https://doi.org/10.1016/j.cels.2021.05.005 -36696816,https://doi.org/10.1016/j.ebiom.2023.104441,Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.,"Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.",,EBioMedicine,2023,2023-01-23,Y,Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation,,,"

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.",,doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render 31196949,https://doi.org/10.1183/13993003.02309-2018,Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children. ,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,The European respiratory journal,2019,2019-09-05,Y,,Improving Public Health,,"The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible. Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators. The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93-2.04), and increased mortality (HR 1.77, 95% CI 1.30-2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49-2.08) and physical (OR 2.76, 95% CI 2.57-2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06-1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24-1.26) partially explained their poorer attainment. Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.",,doi:https://doi.org/10.1183/13993003.02309-2018; html:https://europepmc.org/articles/PMC6727030; pdf:https://europepmc.org/articles/PMC6727030?pdf=render +36696816,https://doi.org/10.1016/j.ebiom.2023.104441,Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.,"Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.",,EBioMedicine,2023,2023-01-23,Y,Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation,,,"

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.",,doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render 37253531,https://doi.org/10.1136/bmjgh-2022-009997,Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.,"Batista-da-Silva AA, Moraes CB, Bozza HR, Bastos LDSL, Ranzani OT, Hamacher S, Bozza FA, Comitê Gestor Conexão Saúde.",,BMJ global health,2023,2023-05-01,Y,"Control strategies; Public Health; Intervention Study; Infections, Diseases, Disorders, Injuries; Covid-19",,,"

Introduction

Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil.

Methods

We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré.

Results

Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset.

Conclusion

An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.",,doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render 30649175,https://doi.org/10.1001/jamacardio.2018.4537,Cardiovascular Risk Factors Associated With Venous Thromboembolism.,"Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després JP, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.",,JAMA cardiology,2019,2019-02-01,Y,,Understanding the Causes of Disease,,"

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.",,doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140 34725404,https://doi.org/10.1038/s41598-021-00748-y,Probabilistic modelling of effects of antibiotics and calendar time on transmission of healthcare-associated infection.,"Laager M, Cooper BS, Eyre DW, CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare).",,Scientific reports,2021,2021-11-01,Y,,,,"Healthcare-associated infection and antimicrobial resistance are major concerns. However, the extent to which antibiotic exposure affects transmission and detection of infections such as MRSA is unclear. Additionally, temporal trends are typically reported in terms of changes in incidence, rather than analysing underling transmission processes. We present a data-augmented Markov chain Monte Carlo approach for inferring changing transmission parameters over time, screening test sensitivity, and the effect of antibiotics on detection and transmission. We expand a basic model to allow use of typing information when inferring sources of infections. Using simulated data, we show that the algorithms are accurate, well-calibrated and able to identify antibiotic effects in sufficiently large datasets. We apply the models to study MRSA transmission in an intensive care unit in Oxford, UK with 7924 admissions over 10 years. We find that falls in MRSA incidence over time were associated with decreases in both the number of patients admitted to the ICU colonised with MRSA and in transmission rates. In our inference model, the data were not informative about the effect of antibiotics on risk of transmission or acquisition of MRSA, a consequence of the limited number of possible transmission events in the data. Our approach has potential to be applied to a range of healthcare-associated infections and settings and could be applied to study the impact of other potential risk factors for transmission. Evidence generated could be used to direct infection control interventions.",,doi:https://doi.org/10.1038/s41598-021-00748-y; html:https://europepmc.org/articles/PMC8560804; pdf:https://europepmc.org/articles/PMC8560804?pdf=render @@ -1678,22 +1680,22 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 31588514,https://doi.org/10.1093/ptj/pzz151,Physical Activity and Sedentary Behavior 6 Months After Musculoskeletal Trauma: What Factors Predict Recovery?,"Ekegren CL, Climie RE, Simpson PM, Owen N, Dunstan DW, Veitch W, Gabbe BJ.",,Physical therapy,2020,2020-02-01,N,,,,"

Background

Physical activity is increasingly recognized as an important marker of functional recovery following fracture.

Objective

The objectives of this study were to measure sedentary behavior and physical activity 2 weeks and 6 months following fracture and to determine associated demographic and injury factors.

Design

This was an observational study.

Methods

Two weeks and 6 months following fracture, 83 adults who were 18 to 69 years old and had upper limb (UL) or lower limb (LL) fractures wore an accelerometer and an inclinometer for 10 days. We calculated sitting time, steps, moderate-intensity physical activity (MPA), and vigorous-intensity physical activity and conducted linear mixed-effects multivariable regression analyses to determine factors associated with temporal changes in activity.

Results

At 6 months versus 2 weeks after fracture, participants sat less, took more steps, and engaged in more MPA. Participants with LL fractures sat 2 hours more, took 66% fewer steps, and engaged in 77% less MPA than participants with UL fractures. Greater reductions in sitting time were observed for participants in the youngest age group and with LL fractures, participants with high preinjury activity, and participants who were overweight or obese. For steps, greater improvement was observed for participants in the youngest and middle-aged groups and those with LL fractures. For MPA, greater improvement was observed for middle-aged participants and those with LL fractures.

Limitations

Although this study was sufficiently powered for the analysis of major categories, a convenience sample that may not be representative of all people with musculoskeletal trauma was used.

Conclusions

Working-age adults with LL fractures had lower levels of physical activity 6 months after fracture than those with UL fractures. Older adults showed less improvement over time, suggesting that they are an important target group for interventions aimed at regaining preinjury activity levels.",,doi:https://doi.org/10.1093/ptj/pzz151 37418234,https://doi.org/10.1007/s12265-023-10403-8,A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.,"Nagyova E, Hoorntje ET, Te Rijdt WP, Bosman LP, Syrris P, Protonotarios A, Elliott PM, Tsatsopoulou A, Mestroni L, Taylor MRG, Sinagra G, Merlo M, Wada Y, Horie M, Mogensen J, Christensen AH, Gerull B, Song L, Yao Y, Fan S, Saguner AM, Duru F, Koskenvuo JW, Cruz Marino T, Tichnell C, Judge DP, Dooijes D, Lekanne Deprez RH, Basso C, Pilichou K, Bauce B, Wilde AAM, Charron P, Fressart V, van der Heijden JF, van den Berg MP, Asselbergs FW, James CA, Jongbloed JDH, Harakalova M, van Tintelen JP.",,Journal of cardiovascular translational research,2023,2023-07-07,N,Genetics; Arrhythmia; Arvc; Composite Endpoint; Multiple Variants; Desmosomal Genes,,,"The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.",,doi:https://doi.org/10.1007/s12265-023-10403-8 35265823,https://doi.org/10.1016/j.eclinm.2022.101317,Variation in global COVID-19 symptoms by geography and by chronic disease: A global survey using the COVID-19 Symptom Mapper.,"Kadirvelu B, Burcea G, Quint JK, Costelloe CE, Faisal AA.",,EClinicalMedicine,2022,2022-03-06,Y,"Comorbidities; Pcr, Polymerase Chain Reaction; Covid-19; Covid-19 Symptoms; Covid Symptom Profile; Covid Symptoms Mapper; Covid Symptoms Survey; Covid-19, The Coronavirus Disease That First Appeared In 2019 Caused By The Sars-cov-2 Coronavirus.; Who, World Health Organization, A Specialized Agency Of The United Nations Responsible For International Public Health.",,,"

Background

COVID-19 is typically characterised by a triad of symptoms: cough, fever and loss of taste and smell, however, this varies globally. This study examines variations in COVID-19 symptom profiles based on underlying chronic disease and geographical location.

Methods

Using a global online symptom survey of 78,299 responders in 190 countries between 09/04/2020 and 22/09/2020, we conducted an exploratory study to examine symptom profiles associated with a positive COVID-19 test result by country and underlying chronic disease (single, co- or multi-morbidities) using statistical and machine learning methods.

Findings

From the results of 7980 COVID-19 tested positive responders, we find that symptom patterns differ by country. For example, India reported a lower proportion of headache (22.8% vs 47.8%, p<1e-13) and itchy eyes (7.3% vs. 16.5%, p=2e-8) than other countries. As with geographic location, we find people differed in their reported symptoms if they suffered from specific chronic diseases. For example, COVID-19 positive responders with asthma (25.3% vs. 13.7%, p=7e-6) were more likely to report shortness of breath compared to those with no underlying chronic disease.

Interpretation

We have identified variation in COVID-19 symptom profiles depending on geographic location and underlying chronic disease. Failure to reflect this symptom variation in public health messaging may contribute to asymptomatic COVID-19 spread and put patients with chronic diseases at a greater risk of infection. Future work should focus on symptom profile variation in the emerging variants of the SARS-CoV-2 virus. This is crucial to speed up clinical diagnosis, predict prognostic outcomes and target treatment.

Funding

We acknowledge funding to AAF by a UKRI Turing AI Fellowship and to CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, Asthma UK-British Lung Foundation, IQVIA, Chiesi AZ, and Insmed. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the Northwest London NIHR Applied Research Collaboration. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.",,doi:https://doi.org/10.1016/j.eclinm.2022.101317; html:https://europepmc.org/articles/PMC8898170; pdf:https://europepmc.org/articles/PMC8898170?pdf=render -35246709,https://doi.org/10.1007/s00127-022-02257-3,Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.,"de Freitas DF, Patel I, Kadra-Scalzo G, Pritchard M, Shetty H, Broadbent M, Patel R, Downs J, Segev A, Khondoker M, MacCabe JH, Bhui K, Hayes RD.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-04,Y,Clozapine; Health Inequalities; Benign Ethnic Neutropenia; Asian British; Black British; Refractory Psychosis,,,"

Purpose

Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder.

Methods

A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use.

Results

Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine.

Conclusion

Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.",,doi:https://doi.org/10.1007/s00127-022-02257-3; html:https://europepmc.org/articles/PMC9246775; pdf:https://europepmc.org/articles/PMC9246775?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02257-3.pdf 34555069,https://doi.org/10.1371/journal.pone.0257361,Predicting fracture outcomes from clinical registry data using artificial intelligence supplemented models for evidence-informed treatment (PRAISE) study protocol.,"Dipnall JF, Page R, Du L, Costa M, Lyons RA, Cameron P, de Steiger R, Hau R, Bucknill A, Oppy A, Edwards E, Varma D, Jung MC, Gabbe BJ.",,PloS one,2021,2021-09-23,Y,,,,"

Background

Distal radius (wrist) fractures are the second most common fracture admitted to hospital. The anatomical pattern of these types of injuries is diverse, with variation in clinical management, guidelines for management remain inconclusive, and the uptake of findings from clinical trials into routine practice limited. Robust predictive modelling, which considers both the characteristics of the fracture and patient, provides the best opportunity to reduce variation in care and improve patient outcomes. This type of data is housed in unstructured data sources with no particular format or schema. The ""Predicting fracture outcomes from clinical Registry data using Artificial Intelligence (AI) Supplemented models for Evidence-informed treatment (PRAISE)"" study aims to use AI methods on unstructured data to describe the fracture characteristics and test if using this information improves identification of key fracture characteristics and prediction of patient-reported outcome measures and clinical outcomes following wrist fractures compared to prediction models based on standard registry data.

Methods and design

Adult (16+ years) patients presenting to the emergency department, treated in a short stay unit, or admitted to hospital for >24h for management of a wrist fracture in four Victorian hospitals will be included in this study. The study will use routine registry data from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), and electronic medical record (EMR) information (e.g. X-rays, surgical reports, radiology reports, images). A multimodal deep learning fracture reasoning system (DLFRS) will be developed that reasons on EMR information. Machine learning prediction models will test the performance with/without output from the DLFRS.

Discussion

The PRAISE study will establish the use of AI techniques to provide enhanced information about fracture characteristics in people with wrist fractures. Prediction models using AI derived characteristics are expected to provide better prediction of clinical and patient-reported outcomes following distal radius fracture.",,doi:https://doi.org/10.1371/journal.pone.0257361; html:https://europepmc.org/articles/PMC8460020; pdf:https://europepmc.org/articles/PMC8460020?pdf=render +35246709,https://doi.org/10.1007/s00127-022-02257-3,Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.,"de Freitas DF, Patel I, Kadra-Scalzo G, Pritchard M, Shetty H, Broadbent M, Patel R, Downs J, Segev A, Khondoker M, MacCabe JH, Bhui K, Hayes RD.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-04,Y,Clozapine; Health Inequalities; Benign Ethnic Neutropenia; Asian British; Black British; Refractory Psychosis,,,"

Purpose

Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder.

Methods

A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use.

Results

Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine.

Conclusion

Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.",,doi:https://doi.org/10.1007/s00127-022-02257-3; html:https://europepmc.org/articles/PMC9246775; pdf:https://europepmc.org/articles/PMC9246775?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02257-3.pdf 31101093,https://doi.org/10.1186/s12889-019-6888-9,Educational and health outcomes of children and adolescents receiving antiepileptic medication: Scotland-wide record linkage study of 766 244 schoolchildren.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,BMC public health,2019,2019-05-17,Y,Epilepsy; Health; Prescribing; Educational Outcomes; Record Linkage; Population Cohort,Improving Public Health,,"

Background

Childhood epilepsy can adversely affect education and employment in addition to health. Previous studies are small or highly selective producing conflicting results. This retrospective cohort study aims to compare educational and health outcomes of children receiving antiepileptic medication versus peers.

Methods

Record linkage of Scotland-wide databases covering dispensed prescriptions, acute and psychiatric hospitalisations, maternity records, deaths, annual pupil census, school absences/exclusions, special educational needs, school examinations, and (un)employment provided data on 766,244 children attending Scottish schools between 2009 and 2013. Outcomes were adjusted for sociodemographic and maternity confounders and comorbid conditions.

Results

Compared with peers, children on antiepileptic medication were more likely to experience school absence (Incidence Rate Ratio [IRR] 1.43, 95% CI: 1.38, 1.48), special educational needs (Odds ratio [OR] 9.60, 95% CI: 9.02, 10.23), achieve the lowest level of attainment (OR 3.43, 95% CI: 2.74, 4.29) be unemployed (OR 1.82, 95% CI: 1.60, 2.07), be admitted to hospital (Hazard Ratio [HR] 3.56, 95% CI: 3.42, 3.70), and die (HR 22.02, 95% CI: 17.00, 28.53). Absenteeism partly explained poorer attainment and higher unemployment. Girls and younger children on antiepileptic medication had higher risk of poor outcomes.

Conclusions

Children on antiepileptic medication fare worse than peers across educational and health outcomes. In order to reduce school absenteeism and mitigate its effects, children with epilepsy should receive integrated care from a multidisciplinary team that spans education and healthcare.",,doi:https://doi.org/10.1186/s12889-019-6888-9; html:https://europepmc.org/articles/PMC6525436; pdf:https://europepmc.org/articles/PMC6525436?pdf=render 33602244,https://doi.org/10.1186/s12916-021-01924-7,The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment.,"Jarvis CI, Gimma A, van Zandvoort K, Wong KLM, CMMID COVID-19 working group, Edmunds WJ.",,BMC medicine,2021,2021-02-19,Y,Pandemic; England; United Kingdom; Disease Outbreak; Non-pharmaceutical Interventions; Covid-19; Contact Survey; Lockdowns,,,"

Background

England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts.

Methods

We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts.

Results

Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3).

Conclusions

The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.",,doi:https://doi.org/10.1186/s12916-021-01924-7; html:https://europepmc.org/articles/PMC7892289; pdf:https://europepmc.org/articles/PMC7892289?pdf=render 33742045,https://doi.org/10.1038/s41598-021-85354-8,Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.,"Roberts HE, Lopopolo M, Pagnamenta AT, Sharma E, Parkes D, Lonie L, Freeman C, Knight SJL, Lunter G, Dreau H, Lockstone H, Taylor JC, Schuh A, Bowden R, Buck D.",,Scientific reports,2021,2021-03-19,Y,,,,"Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.",,doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render 36084617,https://doi.org/10.1016/j.ebiom.2022.104243,Machine learning integration of multimodal data identifies key features of blood pressure regulation.,"Louca P, Tran TQB, Toit CD, Christofidou P, Spector TD, Mangino M, Suhre K, Padmanabhan S, Menni C.",,EBioMedicine,2022,2022-09-06,Y,Diet; Blood pressure; Genomics; Metabolomics; Machine Learning,,,"

Background

Association studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).

Methods

We included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).

Findings

Our model explained 39·2% [4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65)] of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB [SBP variance explained = 45·2% (13·39%)] cohort and 30 of the top 50 features overlapped between cohorts.

Interpretation

We show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.

Funding

Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.",,doi:https://doi.org/10.1016/j.ebiom.2022.104243; html:https://europepmc.org/articles/PMC9463529; pdf:https://europepmc.org/articles/PMC9463529?pdf=render 35301688,https://doi.org/10.1007/s12471-022-01670-2,Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.,"van de Leur RR, Bleijendaal H, Taha K, Mast T, Gho JMIH, Linschoten M, van Rees B, Henkens MTHM, Heymans S, Sturkenboom N, Tio RA, Offerhaus JA, Bor WL, Maarse M, Haerkens-Arends HE, Kolk MZH, van der Lingen ACJ, Selder JJ, Wierda EE, van Bergen PFMM, Winter MM, Zwinderman AH, Doevendans PA, van der Harst P, Pinto YM, Asselbergs FW, van Es R, Tjong FVY, CAPACITY-COVID collaborative consortium.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2022,2022-03-17,Y,Mortality; Electrocardiogram; Arrhythmia; Machine Learning; Deep Learning; Covid-19,,,"

Background and purpose

The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients.

Methods

Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation.

Results

Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block.

Conclusion

This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.",,doi:https://doi.org/10.1007/s12471-022-01670-2; html:https://europepmc.org/articles/PMC8929464; pdf:https://europepmc.org/articles/PMC8929464?pdf=render 31950165,https://doi.org/10.1093/pubmed/fdz188,Is child weight status correctly reported to parents? Cross-sectional analysis of National Child Measurement Programme data using ethnic-specific BMI adjustments.,"Firman N, Boomla K, Hudda MT, Robson J, Whincup P, Dezateux C.",,"Journal of public health (Oxford, England)",2020,2020-11-01,Y,Obesity; Children; Ethnicity,,,"

Background

BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively.

Methods

We used cross-sectional NCMP data (2015-17) for 38 270 children in three inner-London local authorities: City & Hackney, Newham and Tower Hamlets (41% South Asian, 18.8% Black): 20 439 4-5 year-olds (48.9% girls) and 17 831 10-11 year-olds (49.1% girls). We estimated the proportion of parents who would have received different information about their child's weight status, and the area-level prevalence of obesity-defined as ≥98th centile-had ethnic-specific BMI adjustments been employed in the English National Child Measurement Programme (NCMP).

Results

Had ethnic-specific adjustment been employed, 19.7% (3112/15 830) of parents of children from South Asian backgrounds would have been informed that their child was in a heavier weight category, and 19.1% (1381/7217) of parents of children from Black backgrounds would have been informed that their child was in a lighter weight category. Ethnic-specific adjustment increased obesity prevalence from 7.9% (95% CI: 7.6, 8.3) to 9.1% (8.7, 9.5) amongst 4-5 year-olds and from 17.5% (16.9, 18.1) to 18.8% (18.2, 19.4) amongst 10-11 year-olds.

Conclusions

Ethnic-specific adjustment in the NCMP would ensure equitable categorization of weight status, provide correct information to parents and support local service provision for families.",,doi:https://doi.org/10.1093/pubmed/fdz188; html:https://europepmc.org/articles/PMC7685848; pdf:https://europepmc.org/articles/PMC7685848?pdf=render -33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.

Results

We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render +33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.

Results

We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render; pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf 32073627,https://doi.org/10.1093/ije/dyaa002,Educational and health outcomes of children and adolescents receiving antidepressant medication: Scotland-wide retrospective record linkage cohort study of 766 237 schoolchildren.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,International journal of epidemiology,2020,2020-08-01,Y,Depression; Health; Prescribing; Educational Outcomes; Record Linkage; Population Cohort,,,"

Background

Childhood depression is relatively common, under-researched and can impact social and cognitive function and self-esteem.

Methods

Record linkage of routinely collected Scotland-wide administrative databases covering prescriptions [prescribing information system (PIS)], hospitalizations (Scottish Morbidity Records 01 and 04), maternity records (Scottish Morbidity Records 02), deaths (National Records of Scotland), annual pupil census, school absences/exclusions, special educational needs (Scottish Exchange of Educational Data; ScotXed), examinations (Scottish Qualifications Authority) and (un)employment (ScotXed) provided data on 766 237 children attending Scottish schools between 2009 and 2013 inclusively. We compared educational and health outcomes of children receiving antidepressant medication with their peers, adjusting for confounders (socio-demographic, maternity and comorbidity) and explored effect modifiers and mediators.

Results

Compared with peers, children receiving antidepressants were more likely to be absent [adjusted incidence rate ratio (IRR) 1.90, 95% confidence interval (CI) 1.85-1.95] or excluded (adjusted IRR 1.48, 95% CI 1.29-1.69) from school, have special educational needs [adjusted odds ratio (OR) 1.77, 95% CI 1.65-1.90], have the lowest level of academic attainment (adjusted OR 3.00, 95% CI 2.51-3.58) and be unemployed after leaving school (adjusted OR 1.88, 95% CI 1.71-2.08). They had increased hospitalization [adjusted hazard ratio (HR) 2.07, 95% CI 1.98-2.18] and mortality (adjusted HR 2.73, 95% CI 1.73-4.29) over 5 years' follow-up. Higher absenteeism partially explained poorer attainment and unemployment. Treatment with antidepressants was less common among boys than girls (0.5% vs 1.0%) but the associations with special educational need and unemployment were stronger in boys.

Conclusions

Children receiving antidepressants fare worse than their peers across a wide range of education and health outcomes. Interventions to reduce absenteeism or mitigate its effects should be investigated.",,doi:https://doi.org/10.1093/ije/dyaa002; html:https://europepmc.org/articles/PMC7660154; pdf:https://europepmc.org/articles/PMC7660154?pdf=render 33829489,https://doi.org/10.1111/bjd.20140,Defining trajectories of response in patients with psoriasis treated with biologic therapies.,"Geifman N, Azadbakht N, Zeng J, Wilkinson T, Dand N, Buchan I, Stocken D, Di Meglio P, Warren RB, Barker JN, Reynolds NJ, Barnes MR, Smith CH, Griffiths CEM, Peek N, BADBIR Study Group, on behalf of the PSORT Consortium.",,The British journal of dermatology,2021,2021-06-04,N,,,,"

Background

The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.

Objectives

To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.

Methods

We applied latent class mixed modelling to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials.

Results

We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories.

Conclusions

These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.",,doi:https://doi.org/10.1111/bjd.20140 32402553,https://doi.org/10.1016/j.ophtha.2020.03.029,"Visual Field Outcomes from the Multicenter, Randomized Controlled Laser in Glaucoma and Ocular Hypertension Trial (LiGHT).","Wright DM, Konstantakopoulou E, Montesano G, Nathwani N, Garg A, Garway-Heath D, Crabb DP, Gazzard G, Laser in Glaucoma and Ocular Hypertension Trial (LiGHT) Study Group.",,Ophthalmology,2020,2020-04-03,N,,,,"

Purpose

To compare visual field outcomes of ocular hypertensive and glaucoma patients treated first with medical therapy with those treated first with selective laser trabeculoplasty (SLT).

Design

Secondary analysis of patients from the Laser in Glaucoma and Ocular Hypertension study, a multicenter randomized controlled trial.

Participants

Three hundred forty-four patients (588 eyes) treated first with medical therapy and 344 patients (590 eyes) treated first with SLT.

Methods

Visual fields (VFs) were measured using standard automated perimetry and arranged in series (median length and duration, 9 VFs over 48 months). Hierarchical linear models were used to estimate pointwise VF progression rates, which were then averaged to produce a global progression estimate for each eye. Proportions of points and patients in each treatment group with fast (<-1 dB/year) or moderate (<-0.5 dB/year) progression were compared using log-binomial regression.

Main outcome measures

Pointwise and global progression rates of total deviation (TD) and pattern deviation (PD).

Results

A greater proportion of eyes underwent moderate or fast TD progression in the medical therapy group compared with the SLT group (26.2% vs. 16.9%; risk ratio [RR], 1.55; 95% confidence interval [CI], 1.23-1.93; P < 0.001). A similar pattern was observed for pointwise rates (medical therapy, 26.1% vs. SLT, 19.0%; RR, 1.37; 95% CI, 1.33-1.42; P < 0.001). A greater proportion of pointwise PD rates were categorized as moderate or fast in the medical therapy group (medical therapy, 11.5% vs. SLT, 8.3%; RR, 1.39; 95% CI, 1.32-1.46; P < 0.001). No statistical difference was found in the proportion of eyes that underwent moderate or fast PD progression (medical therapy, 9.9% vs. SLT, 7.1%; RR, 1.39; 95% CI, 0.95, 2.03; P = 0.0928).

Conclusions

A slightly larger proportion of ocular hypertensive and glaucoma patients treated first with medical therapy underwent rapid VF progression compared with those treated first with SLT.",,doi:https://doi.org/10.1016/j.ophtha.2020.03.029 30382236,https://doi.org/10.1038/s41433-018-0229-6,The diagnostic accuracy of OCT angiography in naive and treated neovascular age-related macular degeneration: a review.,"Perrott-Reynolds R, Cann R, Cronbach N, Neo YN, Ho V, McNally O, Madi HA, Cochran C, Chakravarthy U.",,"Eye (London, England)",2019,2018-10-31,N,,,,"Optical coherence tomography angiography (OCTA) is a non-invasive retinal imaging innovation that has been gaining popularity for the evaluation of the retinal vasculature. Of clinical importance is its current use either as an alternative or in conjunction with conventional dye-based angiography in neovascular age-related macular degeneration. OCTA is not without limitations and these include image artefact, a relatively small field of view and failure of the segmentation algorithms, which can confound the interpretation of findings. While there are numerous publications on OCTA in neovascular AMD, few have examined the diagnostic accuracy of this new technology compared with the accepted gold standard of fundus fluorescein angiography (FFA). In this review, we summarise the literature on the clinical application of OCTA in nAMD. In particular, we have reviewed the published articles that have reported the sensitivity and specificity of OCTA in the diagnosis of nAMD, and those that have described and or correlated the morphological findings and compared them to dye-based angiography.",Perrott et al. reviewed strengths and limitations of an eye (retinal) imagining method for diagnosis of a condition affecting the central part of the retina (the macula). This degenerative condition may result in loss of central vision in older adults. Perrott et al. concluded that diagnostic accuracy depends on both method and equipment. ,doi:https://doi.org/10.1038/s41433-018-0229-6; html:https://europepmc.org/articles/PMC6367454; pdf:https://europepmc.org/articles/PMC6367454?pdf=render; doi:https://doi.org/10.1038/s41433-018-0229-6 33064085,https://doi.org/10.2196/17003,"Impact of Electronic Health Record Interface Design on Unsafe Prescribing of Ciclosporin, Tacrolimus, and Diltiazem: Cohort Study in English National Health Service Primary Care.","MacKenna B, Bacon S, Walker AJ, Curtis HJ, Croker R, Goldacre B.",,Journal of medical Internet research,2020,2020-10-16,Y,Diltiazem; Prescribing; Ciclosporin; Primary Care; Tacrolimus; Electronic Health Records; Clinical Software; Branded Prescribing,,,"

Background

In England, national safety guidance recommends that ciclosporin, tacrolimus, and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health record (EHR) system interfaces can affect prescribing choices.

Objective

Our objectives were to assess variation by EHR systems in breach of safety guidance around prescribing of ciclosporin, tacrolimus, and diltiazem, and to conduct user-interface research into the causes of such breaches.

Methods

We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective EHR systems. The main outcome measures were (1) the variation in ratio of safety breaches to adherent prescribing in all practices and (2) the description of observations of EHR system usage.

Results

A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus, and diltiazem (over 60 mg); of these, 316,119 prescriptions breached NHS guidance (12.27%). Breaches were most common among users of the EMIS EHR system (breaches in 18.81% of ciclosporin and tacrolimus prescriptions and in 17.99% of diltiazem prescriptions), but breaches were observed in all EHR systems.

Conclusions

Design choices in EHR systems strongly influence safe prescribing of ciclosporin, tacrolimus, and diltiazem, and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system; further quantitative research into the effect of EHR system design on clinical practice is long overdue.",,doi:https://doi.org/10.2196/17003; html:https://europepmc.org/articles/PMC7600019 -32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render 30351417,https://doi.org/10.1093/bioinformatics/bty837,pJRES Binning Algorithm (JBA): a new method to facilitate the recovery of metabolic information from pJRES 1H NMR spectra.,"Rodriguez-Martinez A, Ayala R, Posma JM, Harvey N, Jiménez B, Sonomura K, Sato TA, Matsuda F, Zalloua P, Gauguier D, Nicholson JK, Dumas ME.",,"Bioinformatics (Oxford, England)",2019,2019-06-01,Y,,Applied Analytics,,"

Motivation

Data processing is a key bottleneck for 1H NMR-based metabolic profiling of complex biological mixtures, such as biofluids. These spectra typically contain several thousands of signals, corresponding to possibly few hundreds of metabolites. A number of binning-based methods have been proposed to reduce the dimensionality of 1 D 1H NMR datasets, including statistical recoupling of variables (SRV). Here, we introduce a new binning method, named JBA (""pJRES Binning Algorithm""), which aims to extend the applicability of SRV to pJRES spectra.

Results

The performance of JBA is comprehensively evaluated using 617 plasma 1H NMR spectra from the FGENTCARD cohort. The results presented here show that JBA exhibits higher sensitivity than SRV to detect peaks from low-abundance metabolites. In addition, JBA allows a more efficient removal of spectral variables corresponding to pure electronic noise, and this has a positive impact on multivariate model building.

Availability and implementation

The algorithm is implemented using the MWASTools R/Bioconductor package.

Supplementary information

Supplementary data are available at Bioinformatics online.",,doi:https://doi.org/10.1093/bioinformatics/bty837; html:https://europepmc.org/articles/PMC6546129; pdf:https://europepmc.org/articles/PMC6546129?pdf=render +32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render 37338017,https://doi.org/10.1111/jvh.13863,Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.,"Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",,Journal of viral hepatitis,2023,2023-06-20,N,Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific,,,"Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",,doi:https://doi.org/10.1111/jvh.13863; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863 33407780,https://doi.org/10.1186/s13063-020-04951-6,Reporting guidelines for clinical trials of artificial intelligence interventions: the SPIRIT-AI and CONSORT-AI guidelines.,"Ibrahim H, Liu X, Rivera SC, Moher D, Chan AW, Sydes MR, Calvert MJ, Denniston AK.",,Trials,2021,2021-01-06,Y,Artificial intelligence; Checklist; RANDOMISED CONTROLLED TRIALS; Research Report; Clinical Trials; Guidelines; Research Design; Machine Learning,,,"

Background

The application of artificial intelligence (AI) in healthcare is an area of immense interest. The high profile of 'AI in health' means that there are unusually strong drivers to accelerate the introduction and implementation of innovative AI interventions, which may not be supported by the available evidence, and for which the usual systems of appraisal may not yet be sufficient.

Main text

We are beginning to see the emergence of randomised clinical trials evaluating AI interventions in real-world settings. It is imperative that these studies are conducted and reported to the highest standards to enable effective evaluation because they will potentially be a key part of the evidence that is used when deciding whether an AI intervention is sufficiently safe and effective to be approved and commissioned. Minimum reporting guidelines for clinical trial protocols and reports have been instrumental in improving the quality of clinical trials and promoting completeness and transparency of reporting for the evaluation of new health interventions. The current guidelines-SPIRIT and CONSORT-are suited to traditional health interventions but research has revealed that they do not adequately address potential sources of bias specific to AI systems. Examples of elements that require specific reporting include algorithm version and the procedure for acquiring input data. In response, the SPIRIT-AI and CONSORT-AI guidelines were developed by a multidisciplinary group of international experts using a consensus building methodological process. The extensions include a number of new items that should be reported in addition to the core items. Each item, where possible, was informed by challenges identified in existing studies of AI systems in health settings.

Conclusion

The SPIRIT-AI and CONSORT-AI guidelines provide the first international standards for clinical trials of AI systems. The guidelines are designed to ensure complete and transparent reporting of clinical trial protocols and reports involving AI interventions and have the potential to improve the quality of these clinical trials through improvements in their design and delivery. Their use will help to efficiently identify the safest and most effective AI interventions and commission them with confidence for the benefit of patients and the public.",,doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render 31848017,https://doi.org/10.1016/j.injury.2019.12.016,Pre-injury health status of major trauma patients with orthopaedic injuries.,"Gelaw AY, Gabbe BJ, Simpson PM, Ekegren CL.",,Injury,2020,2019-12-10,N,Trauma; Injury; Quality of life; Health Status; Orthopaedic; Pre-injury,,,"

Background

Pre-injury health status is an important determining factor of long-term outcomes after orthopaedic major trauma. Determining pre-injury health status of major trauma patients with orthopaedic injuries is also important for evaluating the change from pre to post-injury health status.

Objectives

Describe pre-injury health statuses reported at three different time points (6, 12 and 24 months) after injury and compare these with Australian normative values; determine the agreement between pre-injury health status collected at multiple time points post-injury; and identify factors associated with reporting better pre-injury health status.

Materials and methods

A registry-based cohort study was conducted. Major trauma patients with orthopaedic injuries captured by the Victorian State Trauma Registry with a date of injury from January 2009 to December 2016 were included. Pre-injury health status (measured using the EuroQol-Visual Analogue Scale (EQ-VAS)), reported 6, 12 and 24 months post-injury, was compared against Australian population normative values. The Bland-Altman method of comparison was used to determine the agreement between pre-injury EQ-VAS scores reported 6 to 12 and 6 to 24 months post-injury. Mixed effects ordinal logistic regression was used to determine factors associated with reporting better pre-injury health status.

Results

A total of 3,371 patients were eligible for the study. The median (IQR) pre-injury EQ-VAS score reported 6, 12 and 24 months post-injury was 90 (85-100) out of 100. Participants' pre-injury EQ-VAS scores reported 6, 12 and 24 months post-injury were significantly higher than Australian population normative values. Pre-injury EQ-VAS scores reported 6 months post-injury agreed with pre-injury EQ-VAS scores reported 12 and 24 months post-injury. A significant association exists between pre-injury health status and age, comorbidities, injury characteristics, socioeconomic status and pre-injury work status.

Conclusions

People with orthopaedic major trauma have better pre-injury health compared to the general Australian population. Therefore, population-specific values should be used as baseline measures to evaluate orthopaedic trauma outcomes. Pre-injury health status values reported at three different post-injury time points were comparable. If conducting a retrospective pre-injury health evaluation, researchers need be aware of factors that influence self-reporting of pre-injury health status and the response shift that may happen due to encountering injury.",,doi:https://doi.org/10.1016/j.injury.2019.12.016 @@ -1702,12 +1704,12 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 33341984,https://doi.org/10.1111/tme.12750,Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.,"Bell S, Sweeting M, Ramond A, Chung R, Kaptoge S, Walker M, Bolton T, Sambrook J, Moore C, McMahon A, Fahle S, Cullen D, Mehenny S, Wood AM, Armitage J, Ouwehand WH, Miflin G, Roberts DJ, Danesh J, Di Angelantonio E, COMPARE Study Group.",,"Transfusion medicine (Oxford, England)",2021,2020-12-20,Y,Hemocue; Gravimetry; Whole Blood Donor; Non-invasive Haemoglobin Measurement; Haemoglobin Screening; Inappropriate Bleeding; Inappropriate Deferral,,,"

Objective

To compare four haemoglobin measurement methods in whole blood donors.

Background

To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold).

Methods

We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) ""post donation"" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) ""portable haemoglobinometry"" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation (""deferred"") incorrectly; and test preference.

Results

Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry.

Conclusion

In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry.",,doi:https://doi.org/10.1111/tme.12750; html:https://europepmc.org/articles/PMC8048787; pdf:https://europepmc.org/articles/PMC8048787?pdf=render; pdf:https://www.repository.cam.ac.uk/bitstream/1810/315673/1/tme.12750.pdf 33664499,https://doi.org/10.1038/s41431-021-00835-8,Colocalization analysis of polycystic ovary syndrome to identify potential disease-mediating genes and proteins.,"Censin JC, Bovijn J, Holmes MV, Lindgren CM.",,European journal of human genetics : EJHG,2021,2021-03-04,Y,,,,"Polycystic ovary syndrome (PCOS) is a common complex disease in women with a strong genetic component and downstream consequences for reproductive, metabolic and psychological health. There are currently 19 known PCOS risk loci, primarily identified in women of Han Chinese or European ancestry, and 14 of these risk loci were identified or replicated in a genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European descent. However, for most of these loci the gene responsible for the association is unknown. We therefore use a Bayesian colocalization approach (Coloc) to highlight genes in PCOS-associated regions that may have a role in mediating the disease risk. We evaluated the posterior probabilities of evidence consistent with shared causal variants between 14 PCOS genetic risk loci and intermediate cellular phenotypes in one protein (N = 3301) and two expression quantitative trait locus datasets (N = 31,684 and N = 80-491). Through these analyses, we identified seven proteins or genes with evidence of a possibly shared causal variant for almost 30% of known PCOS signals, including follicle stimulating hormone and ERBB3, IKZF4, RPS26, SUOX, ZFP36L2, and C8orf49. Several of these potential effector proteins and genes have been implicated in the hypothalamic-pituitary-gonadal signalling pathway and provide an avenue for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.",,doi:https://doi.org/10.1038/s41431-021-00835-8; html:https://europepmc.org/articles/PMC8440598; pdf:https://europepmc.org/articles/PMC8440598?pdf=render 32678323,https://doi.org/10.1038/s41366-020-0642-3,"Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank.","Zhu P, Lewington S, Haynes R, Emberson J, Landray MJ, Cherney D, Woodward M, Baigent C, Herrington WG, Staplin N.",,International journal of obesity (2005),2020,2020-07-16,Y,,,,"

Background

Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain.

Methods

Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators.

Results

Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53-57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30-34%). Each 5 kg/m2 higher BMI was associated with a 47% (46-49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33-37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure.

Conclusions

Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity-albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.",,doi:https://doi.org/10.1038/s41366-020-0642-3; html:https://europepmc.org/articles/PMC7577847; pdf:https://europepmc.org/articles/PMC7577847?pdf=render -35498042,https://doi.org/10.3389/fcvm.2022.768972,Unravelling the Difference Between Men and Women in Post-CABG Survival.,"Schmidt AF, Haitjema S, Sartipy U, Holzmann MJ, Malenka DJ, Ross CS, van Gilst W, Rouleau JL, Meeder AM, Baker RA, Shiomi H, Kimura T, Tran L, Smith JA, Reid CM, Asselbergs FW, den Ruijter HM.",,Frontiers in cardiovascular medicine,2022,2022-04-13,Y,Atherosclerosis; Sex; Gender; Prognosis; Cabg; Outcome,,,"

Objectives

Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups.

Methods

Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan-Meier estimates, and Cox's proportional hazards model.

Results

During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 × 10-5, respectively), with an effect reversal in younger women.

Conclusion

Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival.",,doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?pdf=render 32135128,https://doi.org/10.1016/s2352-3026(20)30031-4,"Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP): a systematic review and meta-analysis.","Linschoten M, Kamphuis JAM, van Rhenen A, Bosman LP, Cramer MJ, Doevendans PA, Teske AJ, Asselbergs FW.",,The Lancet. Haematology,2020,2020-03-02,N,,,,"BACKGROUND:Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (R-CHOP) or without (CHOP) rituximab is the standard first-line treatment for aggressive non-Hodgkin lymphoma, and doxorubicin and cyclophosphamide are both associated with left ventricular dysfunction. The aim of this systematic review and meta-analysis was to evaluate the cardiovascular toxicity of this regimen. METHODS:We systematically searched PubMed, EMBASE, and the Cochrane Library from database inception to June 3, 2019, for clinical trials and observational studies in adult patients with non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and non-Hodgkin lymphoma not otherwise specified) that received first-line treatment with R-CHOP or CHOP. Studies reporting on cardiovascular adverse events and treatment-related cardiovascular mortality were included. Abstracts and articles not written in English were excluded. The main outcomes were the proportion of patients with grade 3-4 cardiovascular adverse events and heart failure. Meta-analyses of one-sample proportions were done in all patients receiving CHOP or R-CHOP. Subgroup analyses on summary estimates were done to determine the effect of number of CHOP or R-CHOP cycles, cycle interval, age, and sex. FINDINGS:Of 2314 identified entries, 137 studies (21 211 patients) published between April, 1984, and June, 2019 were eligible (9541 patients treated with CHOP, 11 293 patients treated with R-CHOP, 377 both regimens used in the study; median follow-up 39·0 months [IQR 25·5-52·8]). From the included studies, 85 subgroups were treated with CHOP, 76 with R-CHOP, and in four studies both CHOP and R-CHOP were used without a subdivision in separate groups. The pooled proportion for grade 3-4 cardiovascular adverse events, based on 77 studies (n=14 351 patients), was 2·35% (95% CI 1·81-2·93; heterogeneity test Q=326·21; τ2=0·0042; I2=71·40%; p<0·0001). For heart failure, the pooled proportion, based on 38 studies (n=5936 patients), was 4·62% (2·25-7·65; heterogeneity test Q=527·33; τ2=0·0384; I2=95·05%; p<0·0001), with a significant increase in reported heart failure from 1·64% (95% CI 0·82-2·65) to 11·72% (3·00-24·53) when cardiac function was evaluated post-chemotherapy (p=0·017). 53 (39%) of 137 studies were rated as having high risk of bias for incomplete outcome data and 54 (39%) for selective reporting. INTERPRETATION:The considerable increase of reported heart failures with cardiac monitoring, indicates that this complication often remains undiagnosed in patients with non-Hodgkin lymphoma who received first-line R-CHOP or CHOP. Our findings are of importance to raise awareness of this complication among clinicians treating patients with non-Hodgkin lymphoma and stresses the need for cardiac monitoring during and after chemotherapy. Prompt initiation of treatment for heart failure in the presymptomatic phase can mitigate the progression to more advanced heart failure stages. FUNDING:None.",,doi:https://doi.org/10.1016/S2352-3026(20)30031-4 +35498042,https://doi.org/10.3389/fcvm.2022.768972,Unravelling the Difference Between Men and Women in Post-CABG Survival.,"Schmidt AF, Haitjema S, Sartipy U, Holzmann MJ, Malenka DJ, Ross CS, van Gilst W, Rouleau JL, Meeder AM, Baker RA, Shiomi H, Kimura T, Tran L, Smith JA, Reid CM, Asselbergs FW, den Ruijter HM.",,Frontiers in cardiovascular medicine,2022,2022-04-13,Y,Atherosclerosis; Sex; Gender; Prognosis; Cabg; Outcome,,,"

Objectives

Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups.

Methods

Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan-Meier estimates, and Cox's proportional hazards model.

Results

During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 × 10-5, respectively), with an effect reversal in younger women.

Conclusion

Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival.",,doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?pdf=render 34442458,https://doi.org/10.3390/jpm11080814,Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa. ,"Keeler JL, Patsalos O, Chung R, Schmidt U, Breen G, Treasure J, Himmerich H, Dalton B.",,Journal of personalized medicine,2021,2021-08-20,Y,,,,"Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1β were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1β may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.",,doi:https://doi.org/10.3390/jpm11080814; html:https://europepmc.org/articles/PMC8399452; pdf:https://europepmc.org/articles/PMC8399452?pdf=render 35255491,https://doi.org/10.1038/s41586-022-04569-5,SARS-CoV-2 is associated with changes in brain structure in UK Biobank.,"Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM.",,Nature,2022,2022-03-07,Y,,,,"There is strong evidence of brain-related abnormalities in COVID-191-13. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51-81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans-with 141 days on average separating their diagnosis and the second scan-as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.",,doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?pdf=render; pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf -36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render 32808938,https://doi.org/10.2196/17022,Technological Capabilities to Assess Digital Excellence in Hospitals in High Performing Health Care Systems: International eDelphi Exercise.,"Krasuska M, Williams R, Sheikh A, Franklin BD, Heeney C, Lane W, Mozaffar H, Mason K, Eason S, Hinder S, Dunscombe R, Potts HWW, Cresswell K.",,Journal of medical Internet research,2020,2020-08-18,Y,"Delphi Technique; Digital Maturity; Digital Excellence; Hospitals, Ehealth",,,"

Background

Hospitals worldwide are developing ambitious digital transformation programs as part of broader efforts to create digitally advanced health care systems. However, there is as yet no consensus on how best to characterize and assess digital excellence in hospitals.

Objective

Our aim was to develop an international agreement on a defined set of technological capabilities to assess digital excellence in hospitals.

Methods

We conducted a two-stage international modified electronic Delphi (eDelphi) consensus-building exercise, which included a qualitative analysis of free-text responses. In total, 31 international health informatics experts participated, representing clinical, academic, public, and vendor organizations.

Results

We identified 35 technological capabilities that indicate digital excellence in hospitals. These are divided into two categories: (a) capabilities within a hospital (n=20) and (b) capabilities enabling communication with other parts of the health and social care system, and with patients and carers (n=15). The analysis of free-text responses pointed to the importance of nontechnological aspects of digitally enabled change, including social and organizational factors. Examples included an institutional culture characterized by a willingness to transform established ways of working and openness to risk-taking. The availability of a range of skills within digitization teams, including technological, project management and business expertise, and availability of resources to support hospital staff, were also highlighted.

Conclusions

We have identified a set of criteria for assessing digital excellence in hospitals. Our findings highlight the need to broaden the focus from technical functionalities to wider digital transformation capabilities.",,doi:https://doi.org/10.2196/17022; html:https://europepmc.org/articles/PMC7463397 +36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render 32714939,https://doi.org/10.3389/fnut.2020.00080,Future Directions for Integrative Objective Assessment of Eating Using Wearable Sensing Technology.,"Skinner A, Toumpakari Z, Stone C, Johnson L.",,Frontiers in nutrition,2020,2020-07-02,Y,Technology; Assessment; Eating; Objective; Wearable,,,"Established methods for nutritional assessment suffer from a number of important limitations. Diaries are burdensome to complete, food frequency questionnaires only capture average food intake, and both suffer from difficulties in self estimation of portion size and biases resulting from misreporting. Online and app versions of these methods have been developed, but issues with misreporting and portion size estimation remain. New methods utilizing passive data capture are required that address reporting bias, extend timescales for data collection, and transform what is possible for measuring habitual intakes. Digital and sensing technologies are enabling the development of innovative and transformative new methods in this area that will provide a better understanding of eating behavior and associations with health. In this article we describe how wrist-worn wearables, on-body cameras, and body-mounted biosensors can be used to capture data about when, what, and how much people eat and drink. We illustrate how these new techniques can be integrated to provide complete solutions for the passive, objective assessment of a wide range of traditional dietary factors, as well as novel measures of eating architecture, within person variation in intakes, and food/nutrient combinations within meals. We also discuss some of the challenges these new approaches will bring.",,doi:https://doi.org/10.3389/fnut.2020.00080; html:https://europepmc.org/articles/PMC7343846; pdf:https://europepmc.org/articles/PMC7343846?pdf=render 35606419,https://doi.org/10.1038/s41593-022-01074-w,Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging.,"Wang C, Martins-Bach AB, Alfaro-Almagro F, Douaud G, Klein JC, Llera A, Fiscone C, Bowtell R, Elliott LT, Smith SM, Tendler BC, Miller KL.",,Nature neuroscience,2022,2022-05-23,Y,,,,"A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health.",,doi:https://doi.org/10.1038/s41593-022-01074-w; html:https://europepmc.org/articles/PMC9174052; pdf:https://europepmc.org/articles/PMC9174052?pdf=render 32719032,https://doi.org/10.1128/jcm.00670-20,DNA Thermo-Protection Facilitates Whole-Genome Sequencing of Mycobacteria Direct from Clinical Samples. ,"George S, Xu Y, Rodger G, Morgan M, Sanderson ND, Hoosdally SJ, Thulborn S, Robinson E, Rathod P, Walker AS, Peto TEA, Crook DW, Dingle KE.",,Journal of clinical microbiology,2020,2020-09-22,Y,,,,"Mycobacterium tuberculosis is the leading cause of death from bacterial infection. Improved rapid diagnosis and antimicrobial resistance determination, such as by whole-genome sequencing, are required. Our aim was to develop a simple, low-cost method of preparing DNA for sequencing direct from M. tuberculosis-positive clinical samples (without culture). Simultaneous sputum liquefaction, bacteria heat inactivation (99°C/30 min), and enrichment for mycobacteria DNA were achieved using an equal volume of thermo-protection buffer (4 M KCl, 0.05 M HEPES buffer, pH 7.5, 0.1% dithiothreitol [DTT]). The buffer emulated intracellular conditions found in hyperthermophiles, thus protecting DNA from rapid thermodegradation, which renders it a poor template for sequencing. Initial validation experiments employed mycobacteria DNA, either extracted or intracellular. Next, mock clinical samples (infection-negative human sputum spiked with 0 to 105Mycobacterium bovis BCG cells/ml) underwent liquefaction in thermo-protection buffer and heat inactivation. DNA was extracted and sequenced. Human DNA degraded faster than mycobacteria DNA, resulting in target enrichment. Four replicate experiments achieved M. tuberculosis detection at 101 BCG cells/ml, with 31 to 59 M. tuberculosis complex reads. Maximal genome coverage (>97% at 5× depth) occurred at 104 BCG cells/ml; >91% coverage (1× depth) occurred at 103 BCG cells/ml. Final validation employed M. tuberculosis-positive clinical samples (n = 20), revealing that initial sample volumes of ≥1 ml typically yielded higher mean depths of M. tuberculosis genome coverage, with an overall range of 0.55 to 81.02. A mean depth of 3 gave >96% 1-fold tuberculosis (TB) genome coverage (in 15/20 clinical samples). A mean depth of 15 achieved >99% 5-fold genome coverage (in 9/20 clinical samples). In summary, direct-from-sample sequencing of M. tuberculosis genomes was facilitated by a low-cost thermo-protection buffer.",,doi:https://doi.org/10.1128/JCM.00670-20; html:https://europepmc.org/articles/PMC7512152; pdf:https://europepmc.org/articles/PMC7512152?pdf=render @@ -1716,13 +1718,13 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 33910683,https://doi.org/10.1016/j.injury.2021.04.033,"Characteristics, management and outcomes of patients with severe traumatic brain injury in Victoria, Australia compared to United Kingdom and Europe: A comparison between two harmonised prospective cohort studies.","Wiegers EJA, Trapani T, Gabbe BJ, Gantner D, Lecky F, Maas AIR, Menon DK, Murray L, Rosenfeld JV, Vallance S, Lingsma HF, Steyerberg EW, Cooper DJ, CENTER-TBI and OzENTER-TBI investigators and participants12, Collaboration groups: CENTER-TBI and OzENTER-TBI investigators and participants.",,Injury,2021,2021-04-20,N,Traumatic brain injury; Intensive Care; Comparative Effectiveness Research; Trauma Systems; Outcome Comparison,,,"

Objective

The aim of this manuscript is to compare characteristics, management, and outcomes of patients with severe Traumatic Brain Injury (TBI) between Australia, the United Kingdom (UK) and Europe.

Methods

We enrolled patients with severe TBI in Victoria, Australia (OzENTER-TBI), in the UK and Europe (CENTER-TBI) from 2015 to 2017. Main outcome measures were mortality and unfavourable outcome (Glasgow Outcome Scale Extended <5) 6 months after injury. Expected outcomes were compared according to the IMPACT-CT prognostic model, with observed to expected (O/E) ratios and 95% confidence intervals.

Results

We included 107 patients from Australia, 171 from UK, and 596 from Europe. Compared to the UK and Europe, patients in Australia were younger (median 32 vs 44 vs 44 years), a larger proportion had secondary brain insults including hypotension (30% vs 17% vs 21%) and a larger proportion received ICP monitoring (75% vs 74% vs 58%). Hospital length of stay was shorter in Australia than in the UK (median: 17 vs 23 vs 16 days), and a higher proportion of patients were discharged to a rehabilitation unit in Australia than in the UK and Europe (64% vs 26% vs 28%). Mortality overall was lower than expected (27% vs 35%, O/E ratio 0.77 [95% CI: 0.64 - 0.87]. O/E ratios were comparable between regions for mortality in Australia 0.86 [95% CI: 0.49-1.23] vs UK 0.82 [0.51-1.15] vs Europe 0.76 [0.60-0.87]). Unfavourable outcome rates overall were in line with historic expectations (O/E ratio 1.32 [0.96-1.68] vs 1.13 [0.84-1.42] vs 0.96 [0.85-1.09]).

Conclusions

There are major differences in case-mix between Australia, UK, and Europe; Australian patients are younger and have a higher rate of secondary brain insults. Despite some differences in management and discharge policies, mortality was less than expected overall, and did not differ between regions. Functional outcomes were similar between regions, but worse than expected, emphasizing the need to improve treatment for patients with severe TBI.",,doi:https://doi.org/10.1016/j.injury.2021.04.033 34346861,https://doi.org/10.1099/mgen.0.000615,Generalizable characteristics of false-positive bacterial variant calls. ,Bush SJ.,,Microbial genomics,2021,2021-08-01,Y,,,,"Minimizing false positives is a critical issue when variant calling as no method is without error. It is common practice to post-process a variant-call file (VCF) using hard filter criteria intended to discriminate true-positive (TP) from false-positive (FP) calls. These are applied on the simple principle that certain characteristics are disproportionately represented among the set of FP calls and that a user-chosen threshold can maximize the number detected. To provide guidance on this issue, this study empirically characterized all false SNP and indel calls made using real Illumina sequencing data from six disparate species and 166 variant-calling pipelines (the combination of 14 read aligners with up to 13 different variant callers, plus four 'all-in-one' pipelines). We did not seek to optimize filter thresholds but instead to draw attention to those filters of greatest efficacy and the pipelines to which they may most usefully be applied. In this respect, this study acts as a coda to our previous benchmarking evaluation of bacterial variant callers, and provides general recommendations for effective practice. The results suggest that, of the pipelines analysed in this study, the most straightforward way of minimizing false positives would simply be to use Snippy. We also find that a disproportionate number of false calls, irrespective of the variant-calling pipeline, are located in the vicinity of indels, and highlight this as an issue for future development.",,doi:https://doi.org/10.1099/mgen.0.000615; html:https://europepmc.org/articles/PMC8549357; pdf:https://europepmc.org/articles/PMC8549357?pdf=render 37130615,https://doi.org/10.3399/bjgp.2022.0389,Predicting the risk of acute kidney injury in primary care: derivation and validation of STRATIFY-AKI.,"Koshiaris C, Archer L, Lay-Flurrie S, Snell KI, Riley RD, Stevens R, Banerjee A, Usher-Smith JA, Clegg A, Payne RA, Ogden M, Hobbs FR, McManus RJ, Sheppard JP.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-07-27,Y,Blood pressure; Vascular diseases; epidemiology; Primary Health Care; Electronic Health Records; Drug-related Side Effects And Adverse Reactions,,,"

Background

Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks.

Aim

To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment.

Design and setting

Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England.

Method

People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (n = 1 772 618), using a Fine-Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (n = 3 805 322).

Results

The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk.

Conclusion

This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case.",,doi:https://doi.org/10.3399/BJGP.2022.0389; html:https://europepmc.org/articles/PMC10170524; pdf:https://europepmc.org/articles/PMC10170524?pdf=render -32303767,https://doi.org/10.1093/schbul/sbaa040,Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study. ,"Fusar-Poli P, De Micheli A, Patel R, Signorini L, Miah S, Spencer T, McGuire P.",,Schizophrenia bulletin,2020,2020-04-18,N,,,,"The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).",,doi:https://doi.org/10.1093/schbul/sbaa040; html:https://europepmc.org/articles/PMC7505186; pdf:https://europepmc.org/articles/PMC7505186?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa040; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf 29780001,https://doi.org/10.1016/s2352-3026(18)30053-x,Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.,"Lane WJ, Westhoff CM, Gleadall NS, Aguad M, Smeland-Wagman R, Vege S, Simmons DP, Mah HH, Lebo MS, Walter K, Soranzo N, Di Angelantonio E, Danesh J, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Kaufman RM, Rehm HL, Silberstein LE, Green RC, MedSeq Project.",,The Lancet. Haematology,2018,2018-05-17,N,,The Human Phenome,,"

Background

There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens.

Methods

This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.

Findings

We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).

Interpretation

By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.

Funding

National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/S2352-3026(18)30053-X; html:https://europepmc.org/articles/PMC6438177; pdf:https://europepmc.org/articles/PMC6438177?pdf=render; doi:https://doi.org/10.1016/s2352-3026(18)30053-x +32303767,https://doi.org/10.1093/schbul/sbaa040,Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study. ,"Fusar-Poli P, De Micheli A, Patel R, Signorini L, Miah S, Spencer T, McGuire P.",,Schizophrenia bulletin,2020,2020-04-18,N,,,,"The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).",,doi:https://doi.org/10.1093/schbul/sbaa040; html:https://europepmc.org/articles/PMC7505186; pdf:https://europepmc.org/articles/PMC7505186?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa040; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf 32247823,https://doi.org/10.1016/j.jhep.2020.03.032,Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.,"Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-04-02,Y,metabolic syndrome; Magnetic Resonance Imaging; fibrosis; Transaminases; Genome-wide Association Study; Steatohepatitis; Ct1,Understanding the Causes of Disease,oral and gastrointestinal,"

Background & aims

MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.

Methods

First, we performed a genome-wide association study (GWAS) in 14,440 Europeans, with liver cT1 measures, from the UK Biobank. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.

Results

We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p <5×10-8). Four of the variants (rs759359281 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated aminotransferases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and body mass index were causally associated with elevated cT1, whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.

Conclusion

The association between 2 metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at-risk individuals.

Lay summary

We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.",,doi:https://doi.org/10.1016/j.jhep.2020.03.032; html:https://europepmc.org/articles/PMC7372222; pdf:https://europepmc.org/articles/PMC7372222?pdf=render 36204496,https://doi.org/10.1177/23992026211048421,Beyond trust: Amplifying unheard voices on concerns about harm resulting from health data-sharing.,"Mulrine S, Blell M, Murtagh M.",,Medicine access @ point of care,2021,2021-01-01,Y,Data; Qualitative Methods; Data-sharing; Underrepresented Groups,,,"

Background

The point of care in many health systems is increasingly a point of health data generation, data which may be shared and used in a variety of ways by a range of different actors.

Aim

We set out to gather data about the perspectives on health data-sharing of people living in North East England who have been underrepresented within other public engagement activities and who are marginalized in society.

Methods

Multi-site ethnographic fieldwork was carried out in the Teesside region of England over a 6-month period in 2019 as part of a large-scale health data innovation program called Connected Health Cities. Organizations working with marginalized groups were contacted to recruit staff, volunteers, and beneficiaries for participation in qualitative research. The data gathered were analyzed thematically and vignettes constructed to illustrate findings.

Results

Previous encounters with health and social care professionals and the broader socio-political contexts of people's lives shape the perspectives of people from marginalized groups about sharing of data from their health records. While many would welcome improved care, the risks to people with socially produced vulnerabilities must be appreciated by those advocating systems that share data for personalized medicine or other forms of data-driven care.

Conclusion

Forms of innovation in medicine which rely on greater data-sharing may present risks to groups and individuals with existing vulnerabilities, and advocates of these innovations should address the lack of trustworthiness of those receiving data before asking that people trust new systems to provide health benefits.",,doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render 37188768,https://doi.org/10.1038/s42003-023-04836-9,Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.,"Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.",,Communications biology,2023,2023-05-15,Y,,,,"There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.",,doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render -37538507,https://doi.org/10.1016/j.rpth.2023.100175,PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.,"Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",,Research and practice in thrombosis and haemostasis,2023,2023-05-14,Y,Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases,,,"

Background

Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.

Objectives

To reveal new regulatory genes for platelet count (PLT).

Methods

Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.

Results

Of 1588 significantly associated variants (P < 5 × 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K).

Conclusion

Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",,doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render 34740937,https://doi.org/10.1136/bmjopen-2021-056601,Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study.,"Patel R, Smeraldi F, Abdollahyan M, Irving J, Bessant C.",,BMJ open,2021,2021-11-05,Y,information technology; Health Informatics; Covid-19,,,"

Objectives

Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users.

Setting and design

We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19.

Primary outcome measures

(1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities.

Results

Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity.

Conclusions

We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.",,doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render +37538507,https://doi.org/10.1016/j.rpth.2023.100175,PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.,"Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",,Research and practice in thrombosis and haemostasis,2023,2023-05-14,Y,Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases,,,"

Background

Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.

Objectives

To reveal new regulatory genes for platelet count (PLT).

Methods

Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.

Results

Of 1588 significantly associated variants (P < 5 × 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K).

Conclusion

Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",,doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render 34732839,https://doi.org/10.1038/s41379-021-00953-0,Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.,"Stachtea X, Loughrey MB, Salvucci M, Lindner AU, Cho S, McDonough E, Sood A, Graf J, Santamaria-Pang A, Corwin A, Laurent-Puig P, Dasgupta S, Shia J, Owens JR, Abate S, Van Schaeybroeck S, Lawler M, Prehn JHM, Ginty F, Longley DB.",,"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",2022,2021-11-03,Y,,,,"Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as 'high', 'moderate' or 'low', for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1-) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1- Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1- Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1-. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.",,doi:https://doi.org/10.1038/s41379-021-00953-0; html:https://europepmc.org/articles/PMC8964416; pdf:https://europepmc.org/articles/PMC8964416?pdf=render 32724101,https://doi.org/10.1038/s41467-020-17477-x,Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk.,"Huang QQ, Tang HHF, Teo SM, Mok D, Ritchie SC, Nath AP, Brozynska M, Salim A, Bakshi A, Holt BJ, Khor CC, Sly PD, Holt PG, Holt KE, Inouye M.",,Nature communications,2020,2020-07-28,Y,,,,"Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4+ T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identified cis regulatory factors acting as mediators of trans effects. There is extensive colocalisation between condition-specific neonatal cis-eQTLs and variants associated with immune-mediated diseases, in particular CTSH had widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk for BTN3A2, HLA-C and others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases.",,doi:https://doi.org/10.1038/s41467-020-17477-x; html:https://europepmc.org/articles/PMC7387553; pdf:https://europepmc.org/articles/PMC7387553?pdf=render 35477868,https://doi.org/10.1136/bmjopen-2021-057579,Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.,"Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.",,BMJ open,2022,2022-04-27,Y,Information management; Mental health; Health Policy; Health Informatics,,,"

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.",,doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf @@ -1747,26 +1749,26 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 36474045,https://doi.org/10.1038/s41588-022-01233-6,Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.,"Aragam KG, Jiang T, Goel A, Kanoni S, Wolford BN, Atri DS, Weeks EM, Wang M, Hindy G, Zhou W, Grace C, Roselli C, Marston NA, Kamanu FK, Surakka I, Venegas LM, Sherliker P, Koyama S, Ishigaki K, Åsvold BO, Brown MR, Brumpton B, de Vries PS, Giannakopoulou O, Giardoglou P, Gudbjartsson DF, Güldener U, Haider SMI, Helgadottir A, Ibrahim M, Kastrati A, Kessler T, Kyriakou T, Konopka T, Li L, Ma L, Meitinger T, Mucha S, Munz M, Murgia F, Nielsen JB, Nöthen MM, Pang S, Reinberger T, Schnitzler G, Smedley D, Thorleifsson G, von Scheidt M, Ulirsch JC, Biobank Japan, EPIC-CVD, Arnar DO, Burtt NP, Costanzo MC, Flannick J, Ito K, Jang DK, Kamatani Y, Khera AV, Komuro I, Kullo IJ, Lotta LA, Nelson CP, Roberts R, Thorgeirsson G, Thorsteinsdottir U, Webb TR, Baras A, Björkegren JLM, Boerwinkle E, Dedoussis G, Holm H, Hveem K, Melander O, Morrison AC, Orho-Melander M, Rallidis LS, Ruusalepp A, Sabatine MS, Stefansson K, Zalloua P, Ellinor PT, Farrall M, Danesh J, Ruff CT, Finucane HK, Hopewell JC, Clarke R, Gupta RM, Erdmann J, Samani NJ, Schunkert H, Watkins H, Willer CJ, Deloukas P, Kathiresan S, Butterworth AS, CARDIoGRAMplusC4D Consortium.",,Nature genetics,2022,2022-12-06,Y,,,,"The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR-Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.",,doi:https://doi.org/10.1038/s41588-022-01233-6; html:https://europepmc.org/articles/PMC9729111; pdf:https://europepmc.org/articles/PMC9729111?pdf=render 35386118,https://doi.org/10.3389/fnagi.2022.840651,Genome-Wide Association Study of Alzheimer's Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Dataset.,"Homann J, Osburg T, Ohlei O, Dobricic V, Deecke L, Bos I, Vandenberghe R, Gabel S, Scheltens P, Teunissen CE, Engelborghs S, Frisoni G, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Wittig M, Franke A, Lill CM, Blennow K, Zetterberg H, Lovestone S, Streffer J, Ten Kate M, Vos SJB, Barkhof F, Visser PJ, Bertram L.",,Frontiers in aging neuroscience,2022,2022-03-21,Y,X chromosome; MRI; Imaging; Cognitive function; Genome-wide Association Study; Gwas; Alzheimer’s Disease (Ad),,,"Alzheimer's disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.",,doi:https://doi.org/10.3389/fnagi.2022.840651; html:https://europepmc.org/articles/PMC8979334; pdf:https://europepmc.org/articles/PMC8979334?pdf=render 31040096,https://doi.org/10.1016/s2352-4642(19)30114-2,"Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial.","Gilbert R, Brown M, Rainford N, Donohue C, Fraser C, Sinha A, Dorling J, Gray J, McGuire W, Gamble C, Oddie SJ, PREVAIL trial team.",,The Lancet. Child & adolescent health,2019,2019-04-27,N,,"Better, Faster and More Efficient Clinical Trials",,"

Background

Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care.

Methods

This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN, number 81931394.

Findings

Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8·20 days (IQR 4·77-12·13) in the antimicrobial-impregnated PICC group versus 7·86 days (5·00-12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89-1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73-1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16-10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group.

Interpretation

We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection.

Funding

UK National Institute for Health Research Health Technology Assessment programme.",,doi:https://doi.org/10.1016/S2352-4642(19)30114-2 -37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render; doi:https://doi.org/10.1093/eurheartj/ehad260 31810636,https://doi.org/10.1016/j.injury.2019.11.034,Twelve month mortality rates and independent living in people aged 65 years or older after isolated hip fracture: A prospective registry-based study.,"Giummarra MJ, Ekegren CL, Gong J, Simpson P, Cameron PA, Edwards E, Gabbe BJ.",,Injury,2020,2019-11-23,N,Function; Mortality; Recovery; epidemiology; Falls,,,"Introduction:This study investigated which patient and injury characteristics are associated with 12-month mortality rates and living independently after isolated hip fracture.

Methods:Older adults aged ≥65 years were included if they had an isolated hip fracture, were admitted to hospital between July 2009 and June 2016, inclusive, and were registered to the Victorian Orthopaedic Trauma Outcomes Registry. Mortality up to 12 months (365 days) post-injury, and functional outcomes (Glasgow Outcome Scale-Extended; GOS-E) at 12 months post-injury were examined. Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs), and multivariable logistic regression was used to identify predictors of living independently compared with severe disability or death on the GOS-E.

Results:4,912 patients were included, of whom 28% died, 46% had moderate-severe disability, and 26% were living independently 12 months post-injury. Mortality rates were lower in women (aHR=0.56, 95%CI: 0.50, 0.63), and in people injured in a high fall vs low fall (aHR=0.47, 95%CI: 0.31, 0.72). Mortality rates were higher in people in the older age groups (75-84 years: aHR=1.53, 95%CI: 1.21, 1.93; 95+ years: aHR=3.58, 95%CI: 2.68, 4.77), living in areas with the highest level of socioeconomic disadvantage (aHR=1.25, 95%CI: 1.01, 1.55), with a Charlson Comorbidity Index weighting of one (aHR=1.60, 95%CI: 1.36, 1.88) or more than one (aHR=2.21, 95%CI: 1.94, 2.53), whose injury occurred in a residential institution versus at home (aHR=2.63, 95%CI: 1.97, 3.52), that resulted in intensive care unit admission (aHR=1.68, 95%CI: 1.21, 2.32), and in people who did not have surgery versus people who had internal fixation (aHR=1.65, 95%CI: 1.33, 2.04). Independent living was inversely associated with most of the same characteristics; however, people also had lower odds of living independently if they were from metropolitan residential areas versus rural areas (aOR=0.77, 95%CI: 0.62, 0.96), or had mild to moderate (aOR=0.33, 95%CI: 0.27, 0.39) or marked to severe (aOR=0.13, 95%CI: 0.09, 0.20) preinjury disability vs no preinjury disability.

Conclusions:Characteristics that are associated with social disadvantage, frailty, poor health and reduced independence before injury were associated with increased rates of death and reduced odds of living independently 12 months after isolated hip fracture.",,doi:https://doi.org/10.1016/j.injury.2019.11.034 +37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render; doi:https://doi.org/10.1093/eurheartj/ehad260 30949070,https://doi.org/10.3389/fpsyt.2019.00109,Real World Implementation of a Transdiagnostic Risk Calculator for the Automatic Detection of Individuals at Risk of Psychosis in Clinical Routine: Study Protocol.,"Fusar-Poli P, Oliver D, Spada G, Patel R, Stewart R, Dobson R, McGuire P.",,Frontiers in psychiatry,2019,2019-03-13,Y,Schizophrenia; Prevention; risk; Psychosis; Transdiagnostic,"Applied Analytics, Better Care",,"Background: Primary indicated prevention in individuals at-risk for psychosis has the potential to improve the outcomes of this disorder. The ability to detect the majority of at-risk individuals is the main barrier toward extending benefits for the lives of many adolescents and young adults. Current detection strategies are highly inefficient. Only 5% (standalone specialized early detection services) to 12% (youth mental health services) of individuals who will develop a first psychotic disorder can be detected at the time of their at-risk stage. To overcome these challenges a pragmatic, clinically-based, individualized, transdiagnostic risk calculator has been developed to detect individuals at-risk of psychosis in secondary mental health care at scale. This calculator has been externally validated and has demonstrated good prognostic performance. However, it is not known whether it can be used in the real world clinical routine. For example, clinicians may not be willing to adhere to the recommendations made by the transdiagnostic risk calculator. Implementation studies are needed to address pragmatic challenges relating to the real world use of the transdiagnostic risk calculator. The aim of the current study is to provide in-vitro and in-vivo feasibility data to support the implementation of the transdiagnostic risk calculator in clinical routine. Method: This is a study which comprises of two subsequent phases: an in-vitro phase of 1 month and an in-vivo phase of 11 months. The in-vitro phase aims at developing and integrating the transdiagnostic risk calculator in the local electronic health register (primary outcome). The in-vivo phase aims at addressing the clinicians' adherence to the recommendations made by the transdiagnostic risk calculator (primary outcome) and other secondary feasibility parameters that are necessary to estimate the resources needed for its implementation. Discussion: This is the first implementation study for risk prediction models in individuals at-risk for psychosis. Ultimately, successful implementation is the true measure of a prediction model's utility. Therefore, the overall translational deliverable of the current study would be to extend the benefits of primary indicated prevention and improve outcomes of first episode psychosis. This may produce significant social benefits for many adolescents and young adults and their families.",,doi:https://doi.org/10.3389/fpsyt.2019.00109; html:https://europepmc.org/articles/PMC6436079; pdf:https://europepmc.org/articles/PMC6436079?pdf=render 35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Biomedical Ontologies; Data Accuracy; Covid-19; Sars-cov-2; Long Covid; Post–covid-19 Syndrome; Data Extracts; Post–acute Covid-19 Syndrome,,,"

Background

Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.

Objective

We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.

Methods

We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.

Results

In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).

Conclusions

The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859 37286573,https://doi.org/10.1038/s41467-023-38383-y,Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.,"Iglesias MJ, Sanchez-Rivera L, Ibrahim-Kosta M, Naudin C, Munsch G, Goumidi L, Farm M, Smith PM, Thibord F, Kral-Pointner JB, Hong MG, Suchon P, Germain M, Schottmaier W, Dusart P, Boland A, Kotol D, Edfors F, Koprulu M, Pietzner M, Langenberg C, Damrauer SM, Johnson AD, Klarin DM, Smith NL, Smadja DM, Holmström M, Magnusson M, Silveira A, Uhlén M, Renné T, Martinez-Perez A, Emmerich J, Deleuze JF, Antovic J, Soria Fernandez JM, Assinger A, Schwenk JM, Souto Andres JC, Morange PE, Butler LM, Trégouët DA, Odeberg J.",,Nature communications,2023,2023-06-07,Y,,,,"Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.",,doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render -36244350,https://doi.org/10.1016/s2468-2667(22)00225-0,The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.,European Antimicrobial Resistance Collaborators.,,The Lancet. Public health,2022,2022-10-14,Y,,,,"

Background

Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.

Methods

We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings

We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.

Interpretation

The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",,doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253; pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf 31358974,https://doi.org/10.1038/s41562-019-0653-z,New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.,"Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytikäinen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Perälä MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stančáková A, Teumer A, Tuominen S, Thériault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, Männikkö M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, Kähönen M, Kardia SLR, Kühne M, Kuusisto J, Laakso M, Lahti J, Lehtimäki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivières S, Schumann G, Elliott P.",,Nature human behaviour,2019,2019-07-29,N,,,,"Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.",,doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z +36244350,https://doi.org/10.1016/s2468-2667(22)00225-0,The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.,European Antimicrobial Resistance Collaborators.,,The Lancet. Public health,2022,2022-10-14,Y,,,,"

Background

Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.

Methods

We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings

We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.

Interpretation

The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",,doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253; pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf 35322056,https://doi.org/10.1038/s41598-022-08351-5,Automated quality assessment of large digitised histology cohorts by artificial intelligence.,"Haghighat M, Browning L, Sirinukunwattana K, Malacrino S, Khalid Alham N, Colling R, Cui Y, Rakha E, Hamdy FC, Verrill C, Rittscher J.",,Scientific reports,2022,2022-03-23,Y,,,,"Research using whole slide images (WSIs) of histopathology slides has increased exponentially over recent years. Glass slides from retrospective cohorts, some with patient follow-up data are digitised for the development and validation of artificial intelligence (AI) tools. Such resources, therefore, become very important, with the need to ensure that their quality is of the standard necessary for downstream AI development. However, manual quality control of large cohorts of WSIs by visual assessment is unfeasible, and whilst quality control AI algorithms exist, these focus on bespoke aspects of image quality, e.g. focus, or use traditional machine-learning methods, which are unable to classify the range of potential image artefacts that should be considered. In this study, we have trained and validated a multi-task deep neural network to automate the process of quality control of a large retrospective cohort of prostate cases from which glass slides have been scanned several years after production, to determine both the usability of the images at the diagnostic level (considered in this study to be the minimal standard for research) and the common image artefacts present. Using a two-layer approach, quality overlays of WSIs were generated from a quality assessment (QA) undertaken at patch-level at [Formula: see text] magnification. From these quality overlays the slide-level quality scores were predicted and then compared to those generated by three specialist urological pathologists, with a Pearson correlation of 0.89 for overall 'usability' (at a diagnostic level), and 0.87 and 0.82 for focus and H&E staining quality scores respectively. To demonstrate its wider potential utility, we subsequently applied our QA pipeline to the TCGA prostate cancer cohort and to a colorectal cancer cohort, for comparison. Our model, designated as PathProfiler, indicates comparable predicted usability of images from the cohorts assessed (86-90% of WSIs predicted to be usable), and perhaps more significantly is able to predict WSIs that could benefit from an intervention such as re-scanning or re-staining for quality improvement. We have shown in this study that AI can be used to automate the process of quality control of large retrospective WSI cohorts to maximise their utility for research.",,doi:https://doi.org/10.1038/s41598-022-08351-5; html:https://europepmc.org/articles/PMC8943120; pdf:https://europepmc.org/articles/PMC8943120?pdf=render 34441449,https://doi.org/10.3390/diagnostics11081516,Stability of OCT and OCTA in the Intensive Therapy Unit Setting. ,"Courtie EF, Kale AU, Hui BTK, Liu X, Capewell NI, Bishop JRB, Whitehouse T, Veenith T, Logan A, Denniston AK, Blanch RJ.",,"Diagnostics (Basel, Switzerland)",2021,2021-08-23,Y,,,,"To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.",,doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render -35948708,https://doi.org/10.1038/s41586-022-05023-2,Spatially resolved clonal copy number alterations in benign and malignant tissue.,"Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstråhle L, Bergenstråhle J, Larsson L, Alonso Galicia L, Shamikh A, Basmaci E, Díaz De Ståhl T, Rajakumar T, Doultsinos D, Thrane K, Ji AL, Khavari PA, Tarish F, Tanoglidi A, Maaskola J, Colling R, Mirtti T, Hamdy FC, Woodcock DJ, Helleday T, Mills IG, Lamb AD, Lundeberg J.",,Nature,2022,2022-08-10,Y,,,,"Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.",,doi:https://doi.org/10.1038/s41586-022-05023-2; html:https://europepmc.org/articles/PMC9365699; pdf:https://europepmc.org/articles/PMC9365699?pdf=render 30984759,https://doi.org/10.3389/fmed.2019.00048,"Direct-to-Consumer Genetic Testing's Red Herring: ""Genetic Ancestry"" and Personalized Medicine.","Blell M, Hunter MA.",,Frontiers in medicine,2019,2019-03-29,Y,RACE; Ethics; Ethnicity; Genetic Testing; Personalized Medicine,Understanding the Causes of Disease,,"The growth in the direct-to-consumer genetic testing industry poses a number of challenges for healthcare practice, among a number of other areas of concern. Several companies providing this service send their customers reports including information variously referred to as genetic ethnicity, genetic heritage, biogeographic ancestry, and genetic ancestry. In this article, we argue that such information should not be used in healthcare consultations or to assess health risks. Far from representing a move toward personalized medicine, use of this information poses risks both to patients as individuals and to racialized ethnic groups because of the way it misrepresents human genetic diversity.",,doi:https://doi.org/10.3389/fmed.2019.00048; html:https://europepmc.org/articles/PMC6449432; pdf:https://europepmc.org/articles/PMC6449432?pdf=render +35948708,https://doi.org/10.1038/s41586-022-05023-2,Spatially resolved clonal copy number alterations in benign and malignant tissue.,"Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstråhle L, Bergenstråhle J, Larsson L, Alonso Galicia L, Shamikh A, Basmaci E, Díaz De Ståhl T, Rajakumar T, Doultsinos D, Thrane K, Ji AL, Khavari PA, Tarish F, Tanoglidi A, Maaskola J, Colling R, Mirtti T, Hamdy FC, Woodcock DJ, Helleday T, Mills IG, Lamb AD, Lundeberg J.",,Nature,2022,2022-08-10,Y,,,,"Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.",,doi:https://doi.org/10.1038/s41586-022-05023-2; html:https://europepmc.org/articles/PMC9365699; pdf:https://europepmc.org/articles/PMC9365699?pdf=render 33528799,https://doi.org/10.1007/s12471-021-01542-1,Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium.,"Roudijk RW, Taha K, Bourfiss M, Loh P, van den Heuvel L, Boonstra MJ, van Lint F, van der Voorn SM, Te Riele ASJM, Bosman LP, Christiaans I, van Veen TAB, Remme CA, van den Berg MP, van Tintelen JP, Asselbergs FW.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2021,2021-02-02,Y,Dilated cardiomyopathy; Phospholamban; Arrhythmogenic Cardiomyopathy; Pathogenic Variants; Cascade Screening; Plakophilin‑2,,,"In relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy.",,doi:https://doi.org/10.1007/s12471-021-01542-1; html:https://europepmc.org/articles/PMC8160055; pdf:https://europepmc.org/articles/PMC8160055?pdf=render 34371093,https://doi.org/10.1016/j.jaad.2021.07.066,The impact of psoriasis and sexual orientation on mental and physical health among adults in the United States.,"Mansh MD, Mulick A, Langan SM.",,Journal of the American Academy of Dermatology,2022,2021-08-08,Y,,,,,,doi:https://doi.org/10.1016/j.jaad.2021.07.066; html:https://europepmc.org/articles/PMC7612892; pdf:https://europepmc.org/articles/PMC7612892?pdf=render 30014898,https://doi.org/10.1016/j.envres.2018.07.015,Estimation of TETRA radio use in the Airwave Health Monitoring Study of the British police forces.,"Vergnaud AC, Aresu M, Kongsgård HW, McRobie D, Singh D, Spear J, Heard A, Gao H, Carpenter JR, Elliott P.",,Environmental research,2018,2018-07-09,N,Tetra; Occupational Exposure; Occupational Cohort; Radiofrequency Electromagnetic Fields,Improving Public Health,,"

Background

The Airwave Health Monitoring Study aims to investigate the possible long-term health effects of Terrestrial Trunked Radio (TETRA) use among the police forces in Great Britain. Here, we investigate whether objective data from the network operator could be used to correct for misreporting in self-reported data and expand the radio usage availability in our cohort.

Methods

We estimated average monthly usage of personal radio in the 12 months prior to enrolment from a missing value imputation model and evaluated its performance against objective and self-reported data. Factors associated with TETRA radio usage variables were investigated using Chi-square tests and analysis of variance.

Results

The imputed data were better correlated with objective than self-reported usage (Spearman correlation coefficient = 0.72 vs. 0. 52 and kappa 0.56 [95% confidence interval 0.55, 0.56] vs. 0.46 [0.45, 0.47]), although the imputation model tended to under-estimate use for higher users. Participants with higher personal radio usage were more likely to be younger, men vs. women and officer vs. staff. The median average monthly usage level for the entire cohort was estimated to be 29.3 min (95% CI: [7.2, 66.6]).

Conclusion

The availability of objective personal radio records for a large proportion of users allowed us to develop a robust imputation model and hence obtain personal radio usage estimates for ~50,000 participants. This substantially reduced exposure misclassification compared to using self-reported data and will allow us to carry out analyses of TETRA usage for the entire cohort in future work.",,doi:https://doi.org/10.1016/j.envres.2018.07.015 33532905,https://doi.org/10.1007/s12471-021-01539-w,BIO FOr CARE: biomarkers of hypertrophic cardiomyopathy development and progression in carriers of Dutch founder truncating MYBPC3 variants-design and status.,"Jansen M, Christiaans I, van der Crabben SN, Michels M, Huurman R, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, Jans JJM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2021,2021-02-02,Y,Prognosis; Biomarkers; hypertrophic cardiomyopathy; Mybpc3,,,"

Background

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by truncating variants in the MYBPC3 gene. HCM is an important cause of sudden cardiac death; however, overall prognosis is good and penetrance in genotype-positive individuals is incomplete. The underlying mechanisms are poorly understood and risk stratification remains limited.

Aim

To create a nationwide cohort of carriers of truncating MYBPC3 variants for identification of predictive biomarkers for HCM development and progression.

Methods

In the multicentre, observational BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort, carriers of the c.2373dupG, c.2827C > T, c.2864_2865delCT and c.3776delA MYBPC3 variants are included and prospectively undergo longitudinal blood collection. Clinical data are collected from first presentation onwards. The primary outcome constitutes a composite endpoint of HCM progression (maximum wall thickness ≥ 20 mm, septal reduction therapy, heart failure occurrence, sustained ventricular arrhythmia and sudden cardiac death).

Results

So far, 250 subjects (median age 54.9 years (interquartile range 43.3, 66.6), 54.8% male) have been included. HCM was diagnosed in 169 subjects and dilated cardiomyopathy in 4. The primary outcome was met in 115 subjects. Blood samples were collected from 131 subjects.

Conclusion

BIO FOr CARe is a genetically homogeneous, phenotypically heterogeneous cohort incorporating a clinical data registry and longitudinal blood collection. This provides a unique opportunity to study biomarkers for HCM development and prognosis. The established infrastructure can be extended to study other genetic variants. Other centres are invited to join our consortium.",,doi:https://doi.org/10.1007/s12471-021-01539-w; html:https://europepmc.org/articles/PMC8160056; pdf:https://europepmc.org/articles/PMC8160056?pdf=render 34110679,https://doi.org/10.1002/1878-0261.13038,Cost-effectiveness of precision diagnostic testing for precision medicine approaches against non-small-cell lung cancer: A systematic review.,"Henderson R, Keeling P, French D, Smart D, Sullivan R, Lawler M.",,Molecular oncology,2021,2021-07-19,Y,Biomarker; Economic evaluation; non-small-cell lung cancer; Cost-effectiveness Analysis; Precision Medicine; Precision Diagnostic Test,,,"Precision diagnostic testing (PDT) employs appropriate biomarkers to identify cancer patients that may optimally respond to precision medicine (PM) approaches, such as treatments with targeted agents and immuno-oncology drugs. To date, there are no published systematic appraisals evaluating the cost-effectiveness of PDT in non-small-cell lung cancer (NSCLC). To address this gap, we conducted Preferred Reporting Items for Systematic Reviews and Meta-Analyses searches for the years 2009-2019. Consolidated Health Economic Evaluation Reporting Standards were employed to screen, assess and extract data. Employing base costs, life years gained or quality-adjusted life years, as well as willingness-to-pay (WTP) threshold for each country, net monetary benefit was calculated to determine cost-effectiveness of each intervention. Thirty-seven studies (50%) were included for analysis; a further 37 (50%) were excluded, having failed population-, intervention-, comparator-, outcomes- and study-design criteria. Within the 37 studies included, we defined 64 scenarios. Eleven scenarios compared PDT-guided PM with non-guided therapy [epidermal growth factor receptor (EGFR), n = 5; programmed death-ligand 1 (PD-L1), n = 6]. Twenty-eight scenarios compared PDT-guided PM with chemotherapy alone (anaplastic lymphoma kinase, n = 3; EGFR, n = 17; PD-L1, n = 8). Twenty-five scenarios compared PDT-guided PM with chemotherapy alone, while varying the PDT approach. Thirty-four scenarios (53%) were cost-effective, 28 (44%) were not cost-effective, and two were marginal, dependent on their country's WTP threshold. When PDT-guided therapy was compared with a therapy-for-all patients approach, all scenarios (100%) proved cost-effective. Seven of 37 studies had been structured appropriately to assess PDT-PM cost-effectiveness. Within these seven studies, all evaluated scenarios were cost-effective. However, 81% of studies had been poorly designed. Our systematic analysis implies that more robust health economic evaluation could help identify additional approaches towards PDT cost-effectiveness, underpinning value-based care and enhanced outcomes for patients with NSCLC.",,doi:https://doi.org/10.1002/1878-0261.13038; html:https://europepmc.org/articles/PMC8486593; pdf:https://europepmc.org/articles/PMC8486593?pdf=render 32327693,https://doi.org/10.1038/s42003-020-0921-5,Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.,"Oskarsson GR, Oddsson A, Magnusson MK, Kristjansson RP, Halldorsson GH, Ferkingstad E, Zink F, Helgadottir A, Ivarsdottir EV, Arnadottir GA, Jensson BO, Katrinardottir H, Sveinbjornsson G, Kristinsdottir AM, Lee AL, Saemundsdottir J, Stefansdottir L, Sigurdsson JK, Davidsson OB, Benonisdottir S, Jonasdottir A, Jonasdottir A, Jonsson S, Gudmundsson RL, Asselbergs FW, Tragante V, Gunnarsson B, Masson G, Thorleifsson G, Rafnar T, Holm H, Olafsson I, Onundarson PT, Gudbjartsson DF, Norddahl GL, Thorsteinsdottir U, Sulem P, Stefansson K.",,Communications biology,2020,2020-04-23,Y,,,,"Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser = -1.61 SD, CI95 = [-1.98, -1.35]; EffectLys334Ter = 0.63 SD, CI95 = [0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR = 17.1, P = 2 × 10-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.",,doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render -37565978,https://doi.org/10.1016/j.jchf.2023.07.007,Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.,"Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.",,JACC. Heart failure,2023,2023-08-09,N,Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7,,,"

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.",,doi:https://doi.org/10.1016/j.jchf.2023.07.007 35509371,https://doi.org/10.12688/wellcomeopenres.16883.2,Single-cell multi-omics analysis reveals IFN-driven alterations in T lymphocytes and natural killer cells in systemic lupus erythematosus.,"Trzupek D, Lee M, Hamey F, Wicker LS, Todd JA, Ferreira RC.",,Wellcome open research,2021,2021-01-01,Y,Biomarker; Systemic Lupus Erythematosus (Sle); Type I Interferon (Ifn); Multi-omics; Single-cell Rna-sequencing (Scrna-seq); Abseq; Bd Rhapsody; Cytotoxic Cd4+ T Cells (Ctls),,,"Background: The characterisation of the peripheral immune system in the autoimmune disease systemic lupus erythematosus (SLE) at the single-cell level has been limited by the reduced sensitivity of current whole-transcriptomic technologies. Here we employ a targeted single-cell multi-omics approach, combining protein and mRNA quantification, to generate a high-resolution map of the T lymphocyte and natural killer (NK) cell populations in blood from SLE patients. Methods: We designed a custom panel to quantify the transcription of 534 genes in parallel with the expression of 51 surface protein targets using the BD Rhapsody AbSeq single-cell system. We applied this technology to profile 20,656 T and NK cells isolated from peripheral blood from an SLE patient with a type I interferon (IFN)-induced gene expression signature (IFN hi), and an age- and sex- matched IFN low SLE patient and healthy donor. Results: We confirmed the presence of a rare cytotoxic CD4 + T cell (CTL) subset, which was exclusively present in the IFN hi patient. Furthermore, we identified additional alterations consistent with increased immune activation in this patient, most notably a shift towards terminally differentiated CD57 + CD8 + T cell and CD16 + NK dim phenotypes, and the presence of a subset of recently-activated naïve CD4 + T cells. Conclusions: Our results identify IFN-driven changes in the composition and phenotype of T and NK cells that are consistent with a systemic immune activation within the IFN hi patient, and underscore the added resolving power of this multi-omics approach to identify rare immune subsets. Consequently, we were able to find evidence for novel cellular peripheral biomarkers of SLE disease activity, including a subpopulation of CD57 + CD4 + CTLs.",,doi:https://doi.org/10.12688/wellcomeopenres.16883.2; html:https://europepmc.org/articles/PMC9046903; pdf:https://europepmc.org/articles/PMC9046903?pdf=render; pdf:https://wellcomeopenresearch.org/articles/6-149/v2/pdf 32340307,https://doi.org/10.3390/genes11040460,An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data.,"Cipriani V, Pontikos N, Arno G, Sergouniotis PI, Lenassi E, Thawong P, Danis D, Michaelides M, Webster AR, Moore AT, Robinson PN, Jacobsen JOB, Smedley D.",,Genes,2020,2020-04-23,Y,Bioinformatics; Whole-exome Sequencing; Rare Disease; Whole-genome Sequencing; Human Phenotype Ontology; Variant Prioritization; Phenotypic Similarity; Inherited Retinal Disease,,,"Next-generation sequencing has revolutionized rare disease diagnostics, but many patients remain without a molecular diagnosis, particularly because many candidate variants usually survive despite strict filtering. Exomiser was launched in 2014 as a Java tool that performs an integrative analysis of patients' sequencing data and their phenotypes encoded with Human Phenotype Ontology (HPO) terms. It prioritizes variants by leveraging information on variant frequency, predicted pathogenicity, and gene-phenotype associations derived from human diseases, model organisms, and protein-protein interactions. Early published releases of Exomiser were able to prioritize disease-causative variants as top candidates in up to 97% of simulated whole-exomes. The size of the tested real patient datasets published so far are very limited. Here, we present the latest Exomiser version 12.0.1 with many new features. We assessed the performance using a set of 134 whole-exomes from patients with a range of rare retinal diseases and known molecular diagnosis. Using default settings, Exomiser ranked the correct diagnosed variants as the top candidate in 74% of the dataset and top 5 in 94%; not using the patients' HPO profiles (i.e., variant-only analysis) decreased the performance to 3% and 27%, respectively. In conclusion, Exomiser is an effective support tool for rare Mendelian phenotype-driven variant prioritization.",,doi:https://doi.org/10.3390/genes11040460; html:https://europepmc.org/articles/PMC7230372; pdf:https://europepmc.org/articles/PMC7230372?pdf=render +37565978,https://doi.org/10.1016/j.jchf.2023.07.007,Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.,"Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.",,JACC. Heart failure,2023,2023-08-09,N,Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7,,,"

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.",,doi:https://doi.org/10.1016/j.jchf.2023.07.007 33449072,https://doi.org/10.1093/gerona/glab009,Multimorbidity Patterns and Memory Trajectories in Older Adults: Evidence From the English Longitudinal Study of Aging.,"Bendayan R, Zhu Y, Federman AD, Dobson RJB.",,"The journals of gerontology. Series A, Biological sciences and medical sciences",2021,2021-04-01,Y,Longitudinal; Cognitive Decline; Multiple Health Conditions,,,"

Background

We aimed to examine the multimorbidity patterns within a representative sample of UK older adults and their association with concurrent and subsequent memory.

Methods

Our sample consisted of 11 449 respondents (mean age at baseline was 65.02) from the English Longitudinal Study of Aging (ELSA). We used 14 health conditions and immediate and delayed recall scores (IMRC and DLRC) over 7 waves (14 years of follow-up). Latent class analyses were performed to identify the multimorbidity patterns and linear mixed models were estimated to explore their association with their memory trajectories. Models were adjusted by sociodemographics, body mass index (BMI), and health behaviors.

Results

Results showed 8 classes: Class 1: Heart Disease/Stroke (26%), Class 2: Asthma/Lung Disease (16%), Class 3: Arthritis/Hypertension (13%), Class 4: Depression/Arthritis (12%), Class 5: Hypertension/Cataracts/Diabetes (10%), Class 6: Psychiatric Problems/Depression (10%), Class 7: Cancer (7%), and Class 8: Arthritis/Cataracts (6%). At baseline, Class 4 was found to have lower IMRC and DLRC scores and Class 5 in DLRC, compared to the no multimorbidity group (n = 6380, 55.72% of total cohort). For both tasks, in unadjusted models, we found an accelerated decline in Classes 1, 3, and 8; and, for DLRC, also in Classes 2 and 5. However, it was fully attenuated after adjustments.

Conclusions

These findings suggest that individuals with certain combinations of health conditions are more likely to have lower levels of memory compared to those with no multimorbidity and their memory scores tend to differ between combinations. Sociodemographics and health behaviors have a key role to understand who is more likely to be at risk of an accelerated decline.",,doi:https://doi.org/10.1093/gerona/glab009; html:https://europepmc.org/articles/PMC8087269; pdf:https://europepmc.org/articles/PMC8087269?pdf=render 34244281,https://doi.org/10.1136/bmjopen-2021-049611,"Ethnicity and COVID-19 outcomes among healthcare workers in the UK: UK-REACH ethico-legal research, qualitative research on healthcare workers' experiences and stakeholder engagement protocol.","Gogoi M, Reed-Berendt R, Al-Oraibi A, Hassan O, Wobi F, Gupta A, Abubakar I, Dove E, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,BMJ open,2021,2021-07-09,Y,Medical Ethics; Qualitative Research; Medical Law; Covid-19,,,"

Introduction

As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) project has been initiated to generate rapid evidence on whether and why ethnicity affects COVID-19 diagnosis and clinical outcomes in healthcare workers (HCWs) in the UK, through five interlinked work packages/work streams, three of which form the basis of this protocol. The ethico-legal work (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the HCWs' experiences study (Work Package 4) explores their work and personal experiences, perceptions of risk, support and coping mechanisms; the stakeholder engagement work (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations.

Methods and analysis

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

Ethics and dissemination

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

Trial registration number

ISRCTN11811602.",,doi:https://doi.org/10.1136/bmjopen-2021-049611; html:https://europepmc.org/articles/PMC8275361; pdf:https://europepmc.org/articles/PMC8275361?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf 32108548,https://doi.org/10.1177/0269881120907973,Synthetic cannabinoid use in psychiatric patients and relationship to hospitalisation: A retrospective electronic case register study.,"Hobbs M, Patel R, Morrison PD, Kalk N, Stone JM.",,"Journal of psychopharmacology (Oxford, England)",2020,2020-02-28,Y,Cannabis; Psychosis; Hospitalisation; Synthetic Cannabinoids,,,"

Introduction and objectives

Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics and hospitalisation of psychiatric patients who were SC users.

Methods

We searched the Biomedical Research Centre Clinical Record Interactive Search register for SC users and age- and sex-matched SC non-users who had been psychiatric patients under the South London and Maudsley NHS Trust. We recorded diagnosis, homelessness, cannabis use and the total number of days admitted as an inpatient to secondary and tertiary mental-health services.

Results

We identified 635 SC users and 635 age- and sex-matched SC non-users. SC users were significantly more likely to be homeless (χ2=138.0; p<0.0001) and to use cannabis (χ2=257.3; p<0.0001) than SC non-users. SC users had significantly more inpatient days after their first recorded use of SCs than controls (M (SD)=85.5 (199.7) vs. 25.4 (92.32); p<0.0001). Post hoc tests revealed that SC non-users who used cannabis had fewer inpatient days than SC users (p<0.0001), and that non-users of both SC and cannabis had fewer inpatient days than SC non-using cannabis users (p=0.02).

Conclusions

SC use may lead to an increase in the number of days spent in hospital in patients with psychiatric illness. This highlights the need for clinicians to ask specifically about SC use.",,doi:https://doi.org/10.1177/0269881120907973; html:https://europepmc.org/articles/PMC7249610; pdf:https://europepmc.org/articles/PMC7249610?pdf=render @@ -1774,19 +1776,19 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34216337,https://doi.org/10.1007/s10552-021-01466-6,"Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.","Watts EL, Perez-Cornago A, Doherty A, Allen NE, Fensom GK, Tin Tin S, Key TJ, Travis RC.",,Cancer causes & control : CCC,2021,2021-07-03,Y,Testosterone; IGF-I; Physical Activity; Accelerometer; Shbg; Uk Biobank,,,"

Purpose

Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods

Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results

The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion

Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.",,doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render 34788413,https://doi.org/10.1093/ije/dyab149,Data Resource Profile: The Education and Child Health Insights from Linked Data (ECHILD) Database.,"Mc Grath-Lone L, Libuy N, Harron K, Jay MA, Wijlaars L, Etoori D, Lilliman M, Gilbert R, Blackburn R.",,International journal of epidemiology,2022,2022-02-01,Y,Education; Social Care; Adolescent Health; Administrative Data; Linked Data; Key Words: Child Health,,,,,doi:https://doi.org/10.1093/ije/dyab149; html:https://europepmc.org/articles/PMC8856003; pdf:https://europepmc.org/articles/PMC8856003?pdf=render 34455223,https://doi.org/10.1016/j.media.2021.102213,Medical image segmentation automatic quality control: A multi-dimensional approach.,"Fournel J, Bartoli A, Bendahan D, Guye M, Bernard M, Rauseo E, Khanji MY, Petersen SE, Jacquier A, Ghattas B.",,Medical image analysis,2021,2021-08-12,N,Deep Learning; Cmr Image Segmentation; Medical Image Segmentation Automatic Quality Control; Multi-dimensional Quality Control,,,"In clinical applications, using erroneous segmentations of medical images can have dramatic consequences. Current approaches dedicated to medical image segmentation automatic quality control do not predict segmentation quality at slice-level (2D), resulting in sub-optimal evaluations. Our 2D-based deep learning method simultaneously performs quality control at 2D-level and 3D-level for cardiovascular MR image segmentations. We compared it with 3D approaches by training both on 36,540 (2D) / 3842 (3D) samples to predict Dice Similarity Coefficients (DSC) for 4 different structures from the left ventricle, i.e., trabeculations (LVT), myocardium (LVM), papillary muscles (LVPM) and blood (LVC). The 2D-based method outperformed the 3D method. At the 2D-level, the mean absolute errors (MAEs) of the DSC predictions for 3823 samples, were 0.02, 0.02, 0.05 and 0.02 for LVM, LVC, LVT and LVPM, respectively. At the 3D-level, for 402 samples, the corresponding MAEs were 0.02, 0.01, 0.02 and 0.04. The method was validated in a clinical practice evaluation against semi-qualitative scores provided by expert cardiologists for 1016 subjects of the UK BioBank. Finally, we provided evidence that a multi-level QC could be used to enhance clinical measurements derived from image segmentations.",,doi:https://doi.org/10.1016/j.media.2021.102213 -36865374,https://doi.org/10.12688/wellcomeopenres.18175.1,GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.,"Hunter RF, Rodgers SE, Hilton J, Clarke M, Garcia L, Ward Thompson C, Geary R, Green MA, O'Neill C, Longo A, Lovell R, Nurse A, Wheeler BW, Clement S, Porroche-Escudero A, Mitchell R, Barr B, Barry J, Bell S, Bryan D, Buchan I, Butters O, Clemens T, Clewley N, Corcoran R, Elliott L, Ellis G, Guell C, Jurek-Loughrey A, Kee F, Maguire A, Maskell S, Murtagh B, Smith G, Taylor T, Jepson R, GroundsWell Consortium.",,Wellcome open research,2022,2022-09-20,Y,Public Health; Non-Communicable Disease; Green And Blue Space; Complex Systems; Data Science; Citizen Science; Interdisciplinary; Health Inequalities,,,"Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes , with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.",,doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render 34750105,https://doi.org/10.3399/bjgp.2021.0380,OpenSAFELY NHS Service Restoration Observatory 1: primary care clinical activity in England during the first wave of COVID-19.,"Curtis HJ, MacKenna B, Croker R, Inglesby P, Walker AJ, Morley J, Mehrkar A, Morton CE, Bacon S, Hickman G, Bates C, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson EJ, Hulme WJ, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Douglas IJ, Smeeth L, Goldacre B, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2021-12-31,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19,,,"

Background

The COVID-19 pandemic has disrupted healthcare activity. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible.

Aim

To describe the volume and variation of coded clinical activity in general practice, taking respiratory disease and laboratory procedures as examples.

Design and setting

Working on behalf of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY.

Method

Activity using Clinical Terms Version 3 codes and keyword searches from January 2019 to September 2020 are described.

Results

Activity recorded in general practice declined during the pandemic, but largely recovered by September. There was a large drop in coded activity for laboratory tests, with broad recovery to pre-pandemic levels by September. One exception was the international normalised ratio test, with a smaller reduction (median tests per 1000 patients in 2020: February 8.0; April 6.2; September 6.9). The pattern of recording for respiratory symptoms was less affected, following an expected seasonal pattern and classified as 'no change'. Respiratory infections exhibited a sustained drop, not returning to pre-pandemic levels by September. Asthma reviews experienced a small drop but recovered, whereas chronic obstructive pulmonary disease reviews remained below baseline.

Conclusion

An open-source software framework was delivered to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September, with some important tests less affected and recording of respiratory disease codes was mixed.",,doi:https://doi.org/10.3399/BJGP.2021.0380; html:https://europepmc.org/articles/PMC8589464; pdf:https://europepmc.org/articles/PMC8589464?pdf=render -34732073,https://doi.org/10.1161/strokeaha.121.034787,"Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.","Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.",,Stroke,2021,2021-11-04,Y,Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19,,,"

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render +36865374,https://doi.org/10.12688/wellcomeopenres.18175.1,GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.,"Hunter RF, Rodgers SE, Hilton J, Clarke M, Garcia L, Ward Thompson C, Geary R, Green MA, O'Neill C, Longo A, Lovell R, Nurse A, Wheeler BW, Clement S, Porroche-Escudero A, Mitchell R, Barr B, Barry J, Bell S, Bryan D, Buchan I, Butters O, Clemens T, Clewley N, Corcoran R, Elliott L, Ellis G, Guell C, Jurek-Loughrey A, Kee F, Maguire A, Maskell S, Murtagh B, Smith G, Taylor T, Jepson R, GroundsWell Consortium.",,Wellcome open research,2022,2022-09-20,Y,Public Health; Non-Communicable Disease; Green And Blue Space; Complex Systems; Data Science; Citizen Science; Interdisciplinary; Health Inequalities,,,"Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes , with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.",,doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render 31350550,https://doi.org/10.1093/cvr/cvz197,Statistics on mortality following acute myocardial infarction in 842 897 Europeans.,"Alabas OA, Jernberg T, Pujades-Rodriguez M, Rutherford MJ, West RM, Hall M, Timmis A, Lindahl B, Fox KAA, Hemingway H, Gale CP.",,Cardiovascular research,2020,2020-01-01,N,Mortality; Acute myocardial infarction; Sweden; UK; Minap; Swedeheart,,,"

Aims

To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments.

Methods and results

National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 patients, Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)] and the UK [n = 247, 662 529 patients, Myocardial Ischaemia National Audit Project (MINAP)] between 2003 and 2013. There were lower rates of revascularization [STEMI (43.8% vs. 74.9%); NSTEMI (27.5% vs. 43.6%)] and pharmacotherapies at time of hospital discharge including [aspirin (82.9% vs. 90.2%) and (79.9% vs. 88.0%), β-blockers (73.4% vs. 86.4%) and (65.3% vs. 85.1%)] in the UK compared with Sweden, respectively. Standardized net probability of death (NPD) between admission and 1 month was higher in the UK for STEMI [8.0 (95% confidence interval 7.4-8.5) vs. 6.7 (6.5-6.9)] and NSTEMI [6.8 (6.4-7.2) vs. 4.9 (4.7-5.0)]. Between 6 months and 1 year and more than 1 year, NPD remained higher in the UK for NSTEMI [2.9 (2.5-3.3) vs. 2.3 (2.2-2.5)] and [21.4 (20.0-22.8) vs. 18.3 (17.6-19.0)], but was similar for STEMI [0.7 (0.4-1.0) vs. 0.9 (0.7-1.0)] and [8.4 (6.7-10.1) vs. 8.3 (7.5-9.1)].

Conclusion

Short-term mortality following STEMI and NSTEMI was higher in the UK compared with Sweden. Mid- and longer-term mortality remained higher in the UK for NSTEMI but was similar for STEMI. Differences in mortality may be due to differential use of guideline-indicated treatments.",,doi:https://doi.org/10.1093/cvr/cvz197 +34732073,https://doi.org/10.1161/strokeaha.121.034787,"Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.","Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.",,Stroke,2021,2021-11-04,Y,Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19,,,"

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render 35545669,https://doi.org/10.1038/s41586-022-04712-2,Genetic and chemotherapeutic influences on germline hypermutation.,"Kaplanis J, Ide B, Sanghvi R, Neville M, Danecek P, Coorens T, Prigmore E, Short P, Gallone G, McRae J, Genomics England Research Consortium, Carmichael J, Barnicoat A, Firth H, O'Brien P, Rahbari R, Hurles M.",,Nature,2022,2022-05-11,Y,,,,"Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individual's genome1,2. Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 individuals with a hypermutated genome with between two and seven times more de novo single-nucleotide variants than expected. In most families (9 out of 12), the excess mutations came from the father. Two families had genetic drivers of germline hypermutation, with fathers carrying damaging genetic variation in DNA-repair genes. For five of the families, paternal exposure to chemotherapeutic agents before conception was probably a key driver of hypermutation. Our results suggest that the germline is well protected from mutagenic effects, hypermutation is rare, the number of excess mutations is relatively modest and most individuals with a hypermutated genome will not have a genetic disease.",,doi:https://doi.org/10.1038/s41586-022-04712-2; html:https://europepmc.org/articles/PMC9117138; pdf:https://europepmc.org/articles/PMC9117138?pdf=render -34503493,https://doi.org/10.1186/s12916-021-02107-0,"Estimating the impact of reopening schools on the reproduction number of SARS-CoV-2 in England, using weekly contact survey data.","Munday JD, Jarvis CI, Gimma A, Wong KLM, van Zandvoort K, CMMID COVID-19 Working Group, Funk S, Edmunds WJ.",,BMC medicine,2021,2021-09-10,Y,School Closure; Reproduction Number; Social Contacts; Covid-19; Sars-cov-2; Comix,,,"

Background

Schools were closed in England on 4 January 2021 as part of increased national restrictions to curb transmission of SARS-CoV-2. The UK government reopened schools on 8 March. Although there was evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings and the resulting impact on the overall transmission rate in the population were not clear.

Methods

We measured social contacts of > 5000 participants weekly from March 2020, including periods when schools were both open and closed, amongst other restrictions. We combined these data with estimates of the susceptibility and infectiousness of children compared with adults to estimate the impact of reopening schools on the reproduction number.

Results

Our analysis indicates that reopening all schools under the same measures as previous periods that combined lockdown with face-to-face schooling would be likely to increase the reproduction number substantially. Assuming a baseline of 0.8, we estimated a likely increase to between 1.0 and 1.5 with the reopening of all schools or to between 0.9 and 1.2 reopening primary or secondary schools alone.

Conclusion

Our results suggest that reopening schools would likely halt the fall in cases observed between January and March 2021 and would risk a return to rising infections, but these estimates relied heavily on the latest estimates or reproduction number and the validity of the susceptibility and infectiousness profiles we used at the time of reopening.",,doi:https://doi.org/10.1186/s12916-021-02107-0; html:https://europepmc.org/articles/PMC8428960; pdf:https://europepmc.org/articles/PMC8428960?pdf=render 31204027,https://doi.org/10.1016/j.injury.2019.06.012,"Comparing the outcomes of isolated, serious traumatic brain injury in older adults managed at major trauma centres and neurosurgical services: A registry-based cohort study.","Dunn MS, Beck B, Simpson PM, Cameron PA, Kennedy M, Maiden M, Judson R, Gabbe BJ.",,Injury,2019,2019-06-10,N,Traumatic brain injury; Functional Outcome; Older Adult; Tbi; Trauma Systems,,,"

Background

The incidence of older adult traumatic brain injury (TBI) is increasing in both high and middle to low-income countries. It is unknown whether older adults with isolated, serious TBI can be safely managed outside of major trauma centres. This registry based cohort study aimed to compare mortality and functional outcomes of older adults with isolated, serious TBI who were managed at specialised Major Trauma Services (MTS) and Metropolitan Neurosurgical Services (MNS).

Method

Older adults (65 years and over) who sustained an isolated, serious TBI following a low fall (from standing or ≤ 1 m) were extracted from the Victorian State Trauma Registry from 2007 to 2016. Multivariable models were fitted to assess the association between hospital designation (MTS vs. MNS) and the two outcomes of interest: in-hospital mortality and functional outcome, adjusting for potential confounders. Functional outcomes were measured using the Glasgow Outcome Scale Extended at six months post-injury.

Results

From 2007-2016, there were 1904 older adults who sustained an isolated, serious TBI from a low fall who received definitive care at an MTS (n = 1124) or an MNS (n = 780). After adjusting for confounders, there was no mortality benefit for patients managed at an MTS over an MNS (OR = 0.84; 95% CI: 0.65, 1.08; P = 0.17) or improvement in functional outcome six months post-injury (OR = 1.13; 95% CI: 0.94, 1.36; P = 0.21).

Conclusion

For older adults with isolated, serious TBI following a low fall, there was no difference in mortality or functional outcome based on definitive management at an MTS or an MNS. This confirms that MNS without the added designation of a major trauma centre are a suitable destination for the management of isolated, serious TBI in older adults.",,doi:https://doi.org/10.1016/j.injury.2019.06.012 +34503493,https://doi.org/10.1186/s12916-021-02107-0,"Estimating the impact of reopening schools on the reproduction number of SARS-CoV-2 in England, using weekly contact survey data.","Munday JD, Jarvis CI, Gimma A, Wong KLM, van Zandvoort K, CMMID COVID-19 Working Group, Funk S, Edmunds WJ.",,BMC medicine,2021,2021-09-10,Y,School Closure; Reproduction Number; Social Contacts; Covid-19; Sars-cov-2; Comix,,,"

Background

Schools were closed in England on 4 January 2021 as part of increased national restrictions to curb transmission of SARS-CoV-2. The UK government reopened schools on 8 March. Although there was evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings and the resulting impact on the overall transmission rate in the population were not clear.

Methods

We measured social contacts of > 5000 participants weekly from March 2020, including periods when schools were both open and closed, amongst other restrictions. We combined these data with estimates of the susceptibility and infectiousness of children compared with adults to estimate the impact of reopening schools on the reproduction number.

Results

Our analysis indicates that reopening all schools under the same measures as previous periods that combined lockdown with face-to-face schooling would be likely to increase the reproduction number substantially. Assuming a baseline of 0.8, we estimated a likely increase to between 1.0 and 1.5 with the reopening of all schools or to between 0.9 and 1.2 reopening primary or secondary schools alone.

Conclusion

Our results suggest that reopening schools would likely halt the fall in cases observed between January and March 2021 and would risk a return to rising infections, but these estimates relied heavily on the latest estimates or reproduction number and the validity of the susceptibility and infectiousness profiles we used at the time of reopening.",,doi:https://doi.org/10.1186/s12916-021-02107-0; html:https://europepmc.org/articles/PMC8428960; pdf:https://europepmc.org/articles/PMC8428960?pdf=render 35584845,https://doi.org/10.1136/bmj-2022-070904,Reporting guideline for the early stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,BMJ (Clinical research ed.),2022,2022-05-18,Y,,,,,,doi:https://doi.org/10.1136/bmj-2022-070904; html:https://europepmc.org/articles/PMC9116198 34212120,https://doi.org/10.1136/bmjpo-2021-001112,"Incorporating parent, former patient and clinician perspectives in the design of a national UK double-cluster, randomised controlled trial addressing uncertainties in preterm nutrition.","Lammons W, Moss B, Battersby C, Cornelius V, Babalis D, Modi N.",,BMJ paediatrics open,2021,2021-06-15,Y,Neonatology; Qualitative Research; Health Services Research,,,"

Background

Comparative effectiveness randomised controlled trials are powerful tools to resolve uncertainties in existing treatments and care processes. We sought parent and patient perspectives on the design of a planned national, double-cluster randomised controlled trial (COLLABORATE) to resolve two longstanding uncertainties in preterm nutrition.

Methods

We used qualitative focus groups and interviews with parents, former patients and clinicians. We followed the Consolidated Criteria for Reporting Qualitative Research checklist and conducted framework analysis, a specific methodology within thematic analysis.

Results

We identified support for the trial's methodology and vision, and elicited themes illustrating parents' emotional needs in relation to clinical research. These were: relieving the pressure on mothers to breastfeed; opt-out consent as reducing parent stress; the desire for research to be a partnership between clinicians, parents and researchers; the value of presenting trial information in a collaborative tone; and in a format that allows assimilation by parents at their own pace. We identified anxiety and cognitive dissonance among some clinicians in which they recognised the uncertainties that justify the trial but felt unable to participate because of their strongly held views.

Conclusions

The early involvement of parents and former patients identified the centrality of parents' emotional needs in the design of comparative effectiveness research. These insights have been incorporated into trial enrolment processes and information provided to participants. Specific outputs were a two-sided leaflet providing very brief as well as more detailed information, and use of language that parents perceive as inclusive and participatory. Further work is warranted to support clinicians to address personal biases that inhibit trial participation.",,doi:https://doi.org/10.1136/bmjpo-2021-001112; html:https://europepmc.org/articles/PMC8208018; pdf:https://europepmc.org/articles/PMC8208018?pdf=render 31372838,https://doi.org/10.1007/s12471-019-01308-w,"A computerised decision support system for cardiovascular risk management 'live' in the electronic health record environment: development, validation and implementation-the Utrecht Cardiovascular Cohort Initiative.","Groenhof TKJ, Rittersma ZH, Bots ML, Brandjes M, Jacobs JJL, Grobbee DE, van Solinge WW, Visseren FLJ, Haitjema S, Asselbergs FW, Members of the UCC-CVRM Study Group.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2019,2019-09-01,Y,Adherence; Health Information Technology; Big Data; Real-world Data; Cardiovascular Risk Management; Computerised Decision Support System,,,"

Purpose

We set out to develop a real-time computerised decision support system (CDSS) embedded in the electronic health record (EHR) with information on risk factors, estimated risk, and guideline-based advice on treatment strategy in order to improve adherence to cardiovascular risk management (CVRM) guidelines with the ultimate aim of improving patient healthcare.

Methods

We defined a project plan including the scope and requirements, infrastructure and interface, data quality and study population, validation and evaluation of the CDSS.

Results

In collaboration with clinicians, data scientists, epidemiologists, ICT architects, and user experience and interface designers we developed a CDSS that provides 'live' information on CVRM within the environment of the EHR. The CDSS provides information on cardiovascular risk factors (age, sex, medical and family history, smoking, blood pressure, lipids, kidney function, and glucose intolerance measurements), estimated 10-year cardiovascular risk, guideline-compliant suggestions for both pharmacological and non-pharmacological treatment to optimise risk factors, and an estimate on the change in 10-year risk of cardiovascular disease if treatment goals are adhered to. Our pilot study identified a number of issues that needed to be addressed, such as missing data, rules and regulations, privacy, and patient participation.

Conclusion

Development of a CDSS is complex and requires a multidisciplinary approach. We identified opportunities and challenges in our project developing a CDSS aimed at improving adherence to CVRM guidelines. The regulatory environment, including guidance on scientific evaluation, legislation, and privacy issues needs to evolve within this emerging field of eHealth.",,doi:https://doi.org/10.1007/s12471-019-01308-w; html:https://europepmc.org/articles/PMC6712110; pdf:https://europepmc.org/articles/PMC6712110?pdf=render 31782492,https://doi.org/10.1093/ajcn/nqz293,The association of fish consumption and its urinary metabolites with cardiovascular risk factors: the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP).,"Gibson R, Lau CE, Loo RL, Ebbels TMD, Chekmeneva E, Dyer AR, Miura K, Ueshima H, Zhao L, Daviglus ML, Stamler J, Van Horn L, Elliott P, Holmes E, Chan Q.",,The American journal of clinical nutrition,2020,2020-02-01,Y,Hypertension; Blood pressure; FISH; Shellfish; Biomarkers; body mass index; Seafood; Metabonomics; Homarine; Intermap Metabolomics,Improving Public Health,,"

Background

Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent.

Objective

To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations.

Methods

We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40-59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers.

Results

No significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P < 0.0001) and in Western populations between TMAO and BP (diastolic blood pressure: mean difference 1.28; 95% CI: 0.55, 2.02 mmHg; P = 0.0006, systolic blood pressure: mean difference 1.67; 95% CI: 0.60, 2.73 mmHg; P = 0.002).

Conclusions

Urinary TMAO showed a stronger association with fish intake in the Japanese compared with the Western population sample. Urinary TMAO was directly associated with BP in the Western but not the Japanese population sample. Associations between fish intake and its biomarkers and downstream associations with BP/BMI appear to be context specific. INTERMAP is registered at www.clinicaltrials.gov as NCT00005271.",Gibson et al.’s study investigates whether having fish in diet will have an effect on urinary metabolism. They’ve assessed dietary and BP measurement across Asian and Westerns and shown that the relationship was stronger in Japanese population compared to Western population and is highly context dependant. ,doi:https://doi.org/10.1093/ajcn/nqz293; html:https://europepmc.org/articles/PMC6997096; pdf:https://europepmc.org/articles/PMC6997096?pdf=render -35861824,https://doi.org/10.1161/jaha.121.025935,Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.,"Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.",,Journal of the American Heart Association,2022,2022-07-13,Y,Biomarkers; Childhood Cancer Survivors; Cardio‐oncology; Chemokine Ligands; Anthracycline‐related Cardiomyopathy; Cancer Therapy–related Cardiac Dysfunction,,,"Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.",,doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render 31021418,https://doi.org/10.1111/bjd.18046,'It's like the bad guy in a movie who just doesn't die': a qualitative exploration of young people's adaptation to eczema and implications for self-care.,"Ghio D, Muller I, Greenwell K, Roberts A, McNiven A, Langan SM, Santer M.",,The British journal of dermatology,2020,2019-07-28,Y,,,,"

Background

Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children 'outgrow eczema', although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course.

Objectives

To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self-care and adapting to living with eczema.

Methods

This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old.

Results

Participants generally experienced eczema as an episodic long-term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self-care, challenging the process of identifying triggers of eczema flare-ups and evaluating the success of treatment regimens. Participants' experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from 'cure' to 'control' of eczema.

Conclusions

For young people who continue to experience eczema beyond childhood, a greater focus on self-care for a long-term condition may be helpful. Greater awareness of the impact of early messages around 'growing out of' eczema and provision of high-quality information may help patients to manage expectations and support adaptation to treatment regimens. What's already known about this topic? There is a common perception that people 'grow out of' eczema, but for many people eczema follows a lifelong episodic course. Qualitative work has shown that parents can find that being told their child will grow out of eczema is dismissive, and that they have difficulty with messages about 'control not cure' of eczema. It is unclear how young people perceive their eczema and the implications of this perception for their adaptation and self-care. What does this study add? The message that many people 'grow out of' eczema has a potentially detrimental effect for young people where the condition persists. This has implications for young people's perceptions of their eczema, their learning to self-care and how they adapt to living with eczema and eczema treatments. What are the clinical implications of this work? Clinicians need to promote awareness among young people that eczema is a long-term episodic condition in order to engage them with effective self-care. Young people transitioning to self-care need evidence-based information that is specific and relatable to them.", ,doi:https://doi.org/10.1111/bjd.18046; html:https://europepmc.org/articles/PMC6972719; pdf:https://europepmc.org/articles/PMC6972719?pdf=render +35861824,https://doi.org/10.1161/jaha.121.025935,Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.,"Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.",,Journal of the American Heart Association,2022,2022-07-13,Y,Biomarkers; Childhood Cancer Survivors; Cardio‐oncology; Chemokine Ligands; Anthracycline‐related Cardiomyopathy; Cancer Therapy–related Cardiac Dysfunction,,,"Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.",,doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render 35908569,https://doi.org/10.1016/s0140-6736(22)01109-6,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-07-01,Y,,,,"

Background

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

Methods

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

Findings

Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render; pdf:http://www.thelancet.com/article/S0140673622011096/pdf 32576090,https://doi.org/10.1161/strokeaha.120.029042,Telemedicine Cognitive Behavioral Therapy for Anxiety After Stroke: Proof-of-Concept Randomized Controlled Trial.,"Chun HY, Carson AJ, Tsanas A, Dennis MS, Mead GE, Calabria C, Whiteley WN.",,Stroke,2020,2020-06-24,Y,Stroke; Anxiety; Workflow; Telemedicine; psychotherapy,,,"

Background and purpose

Disabling anxiety affects a quarter of stroke survivors but access to treatment is poor. We developed a telemedicine model for delivering guided self-help cognitive behavioral therapy (CBT) for anxiety after stroke (TASK-CBT). We aimed to evaluate the feasibility of TASK-CBT in a randomized controlled trial workflow that enabled all trial procedures to be carried out remotely. In addition, we explored the feasibility of wrist-worn actigraphy sensor as a way of measuring objective outcomes in this clinical trial.

Methods

We recruited adult community-based stroke patients (n=27) and randomly allocated them to TASK-CBT (n=14) or relaxation therapy (TASK-Relax), an active comparator (n=13).

Results

In our sample (mean age 65 [±10]; 56% men; 63% stroke, 37% transient ischemic attacks), remote self-enrolment, electronic signature, intervention delivery, and automated follow-up were feasible. All participants completed all TASK-CBT sessions (14/14). Lower levels of anxiety were observed in TASK-CBT when compared with TASK-Relax at both weeks 6 and 20. Mean actigraphy sensor wearing-time was 33 days (±15).

Conclusions

Our preliminary feasibility data from the current study support a larger definitive clinical trial and the use of wrist-worn actigraphy sensor in anxious stroke survivors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03439813.",,doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?pdf=render 33664493,https://doi.org/10.1038/s41591-021-01275-z,The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice.,"Cruz Rivera S, Mercieca-Bebber R, Aiyegbusi OL, Scott J, Hunn A, Fernandez C, Ives J, Ells C, Price G, Draper H, Calvert MJ.",,Nature medicine,2021,2021-04-01,N,,,,,,doi:https://doi.org/10.1038/s41591-021-01275-z @@ -1794,21 +1796,21 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 31950891,https://doi.org/10.1192/bjo.2019.96,Predicting high-cost care in a mental health setting.,"Colling C, Khondoker M, Patel R, Fok M, Harland R, Broadbent M, McCrone P, Stewart R.",,BJPsych open,2020,2020-01-17,Y,Prediction; Natural Language Processing; Mental Health Service; Digital Health Records,,,"

Background

The density of information in digital health records offers new potential opportunities for automated prediction of cost-relevant outcomes.

Aims

We investigated the extent to which routinely recorded data held in the electronic health record (EHR) predict priority service outcomes and whether natural language processing tools enhance the predictions. We evaluated three high priority outcomes: in-patient duration, readmission following in-patient care and high service cost after first presentation.

Method

We used data obtained from a clinical database derived from the EHR of a large mental healthcare provider within the UK. We combined structured data with text-derived data relating to diagnosis statements, medication and psychiatric symptomatology. Predictors of the three different clinical outcomes were modelled using logistic regression with performance evaluated against a validation set to derive areas under receiver operating characteristic curves.

Results

In validation samples, the full models (using all available data) achieved areas under receiver operating characteristic curves between 0.59 and 0.85 (in-patient duration 0.63, readmission 0.59, high service use 0.85). Adding natural language processing-derived data to the models increased the variance explained across all clinical scenarios (observed increase in r2 = 12-46%).

Conclusions

EHR data offer the potential to improve routine clinical predictions by utilising previously inaccessible data. Of our scenarios, prediction of high service use after initial presentation achieved the highest performance.","This study uses data from a mental healthcare provider to predict 3 things: 1) extended duration of stay in a hospital, 2) the likelihood of needing to be admitted to hospital again after discharge, and 3) likehood of needing 'high intesity service' (high cost services). The authors developed a natural language processing model (a computer system than aims to interpret text and draw out useful information) to review the text, diagnoses, medications and the patient symptoms to work out which patients would fall within those 3 categories. They conclude that their model could be used to improve services through predicting users who will require the most intense and costly care.",doi:https://doi.org/10.1192/bjo.2019.96; html:https://europepmc.org/articles/PMC7001466; pdf:https://europepmc.org/articles/PMC7001466?pdf=render 33436814,https://doi.org/10.1038/s41598-020-80457-0,A natural language processing approach for identifying temporal disease onset information from mental healthcare text.,"Viani N, Botelle R, Kerwin J, Yin L, Patel R, Stewart R, Velupillai S.",,Scientific reports,2021,2021-01-12,Y,,,,"Receiving timely and appropriate treatment is crucial for better health outcomes, and research on the contribution of specific variables is essential. In the mental health domain, an important research variable is the date of psychosis symptom onset, as longer delays in treatment are associated with worse intervention outcomes. The growing adoption of electronic health records (EHRs) within mental health services provides an invaluable opportunity to study this problem at scale retrospectively. However, disease onset information is often only available in open text fields, requiring natural language processing (NLP) techniques for automated analyses. Since this variable can be documented at different points during a patient's care, NLP methods that model clinical and temporal associations are needed. We address the identification of psychosis onset by: 1) manually annotating a corpus of mental health EHRs with disease onset mentions, 2) modelling the underlying NLP problem as a paragraph classification approach, and 3) combining multiple onset paragraphs at the patient level to generate a ranked list of likely disease onset dates. For 22/31 test patients (71%) the correct onset date was found among the top-3 NLP predictions. The proposed approach was also applied at scale, allowing an onset date to be estimated for 2483 patients.",,doi:https://doi.org/10.1038/s41598-020-80457-0; html:https://europepmc.org/articles/PMC7804184; pdf:https://europepmc.org/articles/PMC7804184?pdf=render 36608816,https://doi.org/10.1016/j.diabet.2022.101418,Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.,"Karasik A, Lanzinger S, Chia-Hui Tan E, Yabe D, Kim DJ, Sheu WH, Melzer-Cohen C, Holl RW, Ha KH, Khunti K, Zaccardi F, Subramanian A, Nirantharakumar K, Nyström T, Niskanen L, Linnemann Jensen M, Hoti F, Klement R, Déruaz-Luyet A, Kyaw MH, Koeneman L, Vistisen D, Carstensen B, Halvorsen S, Langslet G, Fazeli Farsani S, Patorno E, Núñez J, EMPRISE Europe and Asia Study Group.",,Diabetes & metabolism,2023,2023-01-03,N,Cardiovascular diseases; Meta-analysis; Heart Failure; All-cause Mortality; Pharmacoepidemiology; Observational Study; Comparative Effectiveness; Dipeptidyl Peptidase-4 Inhibitors; Empagliflozin; Sodium-glucose Transporter 2 Inhibitors,,,"

Background

Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.

Methods

The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined.

Findings

Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions.

Interpretation

Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.",,doi:https://doi.org/10.1016/j.diabet.2022.101418 -33012285,https://doi.org/10.1186/s12916-020-01779-4,The impact of COVID-19 control measures on social contacts and transmission in Kenyan informal settlements.,"Quaife M, van Zandvoort K, Gimma A, Shah K, McCreesh N, Prem K, Barasa E, Mwanga D, Kangwana B, Pinchoff J, CMMID COVID-19 Working Group, Edmunds WJ, Jarvis CI, Austrian K.",,BMC medicine,2020,2020-10-05,Y,Social Contacts; Covid-19; Sars-cov-2; Physical Distancing,,,"

Background

Many low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study, we collect contact data from residents of informal settlements around Nairobi, Kenya, to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number (R0).

Methods

We conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, 4 weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7 pm and 5 am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R0.

Results

We estimate that control measures reduced physical contacts by 62% and non-physical contacts by either 63% or 67%, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. Eighty-six percent of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food.

Conclusion

COVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R0 are consistent with the comparatively low epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term.",,doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render 32784218,https://doi.org/10.3399/bjgp20x712313,Suboptimal prescribing behaviour associated with clinical software design features: a retrospective cohort study in English NHS primary care.,"MacKenna B, Curtis HJ, Walker AJ, Bacon S, Croker R, Goldacre B.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2020,2020-08-27,N,Cohort studies; Primary Care; Clinical Software; Ghost-branded Generics; Drugs Prescribing,,,"

Background

Electronic health record (EHR) systems are used by clinicians to record patients' medical information, and support clinical activities such as prescribing. In England, healthcare professionals are advised to 'prescribe generically' because generic drugs are usually cheaper than branded alternatives, and have fixed reimbursement costs. 'Ghost-branded generics' are a new category of medicines savings, caused by prescribers specifying a manufacturer for a generic product, often resulting in a higher reimbursement price compared with the true generic.

Aim

To describe time trends and practice factors associated with excess medication costs from ghost-branded generic prescribing.

Design and setting

Retrospective cohort study of English GP prescribing data and EHR deployment data.

Method

A retrospective cohort study was conducted, based on data from the OpenPrescribing.net database from May 2013 to May 2019. Total spending on ghost-branded generics across England was calculated, and excess spend on ghost-branded generics calculated as a percentage of all spending on generics for every CCG and general practice in England, for every month in the study period.

Results

There were 31.8 million ghost-branded generic items and £9.5 million excess cost in 2018, compared with 7.45 million ghost-branded generic items and £1.3 million excess cost in 2014. Most excess costs were associated with one EHR, SystmOne, and it was identified that SystmOne offered ghost-branded generic options as the default. After informing the vendor, the authors monitored for subsequent change in costs, and report a rapid decrease in ghost-branded generic expenditure.

Conclusion

A design choice in a commonly used EHR has led to £9.5 million in avoidable excess prescribing costs for the NHS in 1 year. Notifying the vendor led to a change in user interface and a rapid, substantial spend reduction. This finding illustrates that EHR user interface design has a substantial impact on the quality, safety, and cost-effectiveness of clinical practice; this should be a priority for quantitative research.",,doi:https://doi.org/10.3399/bjgp20X712313; html:https://europepmc.org/articles/PMC7425205; pdf:https://europepmc.org/articles/PMC7425205?pdf=render; doi:https://doi.org/10.3399/bjgp20x712313 +33012285,https://doi.org/10.1186/s12916-020-01779-4,The impact of COVID-19 control measures on social contacts and transmission in Kenyan informal settlements.,"Quaife M, van Zandvoort K, Gimma A, Shah K, McCreesh N, Prem K, Barasa E, Mwanga D, Kangwana B, Pinchoff J, CMMID COVID-19 Working Group, Edmunds WJ, Jarvis CI, Austrian K.",,BMC medicine,2020,2020-10-05,Y,Social Contacts; Covid-19; Sars-cov-2; Physical Distancing,,,"

Background

Many low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study, we collect contact data from residents of informal settlements around Nairobi, Kenya, to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number (R0).

Methods

We conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, 4 weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7 pm and 5 am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R0.

Results

We estimate that control measures reduced physical contacts by 62% and non-physical contacts by either 63% or 67%, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. Eighty-six percent of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food.

Conclusion

COVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R0 are consistent with the comparatively low epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term.",,doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render +32656368,https://doi.org/10.12688/wellcomeopenres.15889.2,What settings have been linked to SARS-CoV-2 transmission clusters?,"Leclerc QJ, Fuller NM, Knight LE, CMMID COVID-19 Working Group, Funk S, Knight GM.",,Wellcome open research,2020,2020-06-05,Y,Transmission; Cluster; Coronavirus; Settings; Lockdown; Covid-19; Sars-cov-2,,,"Background: Concern about the health impact of novel coronavirus SARS-CoV-2 has resulted in widespread enforced reductions in people's movement (""lockdowns""). However, there are increasing concerns about the severe economic and wider societal consequences of these measures. Some countries have begun to lift some of the rules on physical distancing in a stepwise manner, with differences in what these ""exit strategies"" entail and their timeframes. The aim of this work was to inform such exit strategies by exploring the types of indoor and outdoor settings where transmission of SARS-CoV-2 has been reported to occur and result in clusters of cases. Identifying potential settings that result in transmission clusters allows these to be kept under close surveillance and/or to remain closed as part of strategies that aim to avoid a resurgence in transmission following the lifting of lockdown measures. Methods: We performed a systematic review of available literature and media reports to find settings reported in peer reviewed articles and media with these characteristics. These sources are curated and made available in an editable online database. Results: We found many examples of SARS-CoV-2 clusters linked to a wide range of mostly indoor settings. Few reports came from schools, many from households, and an increasing number were reported in hospitals and elderly care settings across Europe. Conclusions: We identified possible places that are linked to clusters of COVID-19 cases and could be closely monitored and/or remain closed in the first instance following the progressive removal of lockdown restrictions. However, in part due to the limits in surveillance capacities in many settings, the gathering of information such as cluster sizes and attack rates is limited in several ways: inherent recall bias, biased media reporting and missing data.",,doi:https://doi.org/10.12688/wellcomeopenres.15889.2; html:https://europepmc.org/articles/PMC7327724; pdf:https://europepmc.org/articles/PMC7327724?pdf=render 34645462,https://doi.org/10.1186/s12974-021-02287-9,T lymphocyte senescence is attenuated in Parkinson's disease.,"Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH.",,Journal of neuroinflammation,2021,2021-10-13,Y,T lymphocytes; Immunosenescence; Parkinson’s Disease; Ageing Markers,,,"

Background

Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes.

Methods

Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1.

Results

The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients.

Conclusions

Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.",,doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render 35962208,https://doi.org/10.1038/s41591-022-01951-8,Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-10-01,N,,,,,,doi:https://doi.org/10.1038/s41591-022-01951-8; pdf:https://www.nature.com/articles/s41591-022-01951-8.pdf -32656368,https://doi.org/10.12688/wellcomeopenres.15889.2,What settings have been linked to SARS-CoV-2 transmission clusters?,"Leclerc QJ, Fuller NM, Knight LE, CMMID COVID-19 Working Group, Funk S, Knight GM.",,Wellcome open research,2020,2020-06-05,Y,Transmission; Cluster; Coronavirus; Settings; Lockdown; Covid-19; Sars-cov-2,,,"Background: Concern about the health impact of novel coronavirus SARS-CoV-2 has resulted in widespread enforced reductions in people's movement (""lockdowns""). However, there are increasing concerns about the severe economic and wider societal consequences of these measures. Some countries have begun to lift some of the rules on physical distancing in a stepwise manner, with differences in what these ""exit strategies"" entail and their timeframes. The aim of this work was to inform such exit strategies by exploring the types of indoor and outdoor settings where transmission of SARS-CoV-2 has been reported to occur and result in clusters of cases. Identifying potential settings that result in transmission clusters allows these to be kept under close surveillance and/or to remain closed as part of strategies that aim to avoid a resurgence in transmission following the lifting of lockdown measures. Methods: We performed a systematic review of available literature and media reports to find settings reported in peer reviewed articles and media with these characteristics. These sources are curated and made available in an editable online database. Results: We found many examples of SARS-CoV-2 clusters linked to a wide range of mostly indoor settings. Few reports came from schools, many from households, and an increasing number were reported in hospitals and elderly care settings across Europe. Conclusions: We identified possible places that are linked to clusters of COVID-19 cases and could be closely monitored and/or remain closed in the first instance following the progressive removal of lockdown restrictions. However, in part due to the limits in surveillance capacities in many settings, the gathering of information such as cluster sizes and attack rates is limited in several ways: inherent recall bias, biased media reporting and missing data.",,doi:https://doi.org/10.12688/wellcomeopenres.15889.2; html:https://europepmc.org/articles/PMC7327724; pdf:https://europepmc.org/articles/PMC7327724?pdf=render 35017564,https://doi.org/10.1038/s41467-021-27950-w,Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.,"Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM.",,Nature communications,2022,2022-01-11,Y,,,,"Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.",,doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render -37034358,https://doi.org/10.1016/j.eclinm.2023.101932,Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.,"Voss EA, Shoaibi A, Yin Hui Lai L, Blacketer C, Alshammari T, Makadia R, Haynes K, Sena AG, Rao G, van Sandijk S, Fraboulet C, Boyer L, Le Carrour T, Horban S, Morales DR, Martínez Roldán J, Ramírez-Anguita JM, Mayer MA, de Wilde M, John LH, Duarte-Salles T, Roel E, Pistillo A, Kolde R, Maljković F, Denaxas S, Papez V, Kahn MG, Natarajan K, Reich C, Secora A, Minty EP, Shah NH, Posada JD, Garcia Morales MT, Bosca D, Cadenas Juanino H, Diaz Holgado A, Pedrera Jiménez M, Serrano Balazote P, García Barrio N, Şen S, Üresin AY, Erdogan B, Belmans L, Byttebier G, Malbrain MLNG, Dedman DJ, Cuccu Z, Vashisht R, Butte AJ, Patel A, Dahm L, Han C, Bu F, Arshad F, Ostropolets A, Nyberg F, Hripcsak G, Suchard MA, Prieto-Alhambra D, Rijnbeek PR, Schuemie MJ, Ryan PB.",,EClinicalMedicine,2023,2023-04-04,Y,Observational Research; Omop Cdm; Covid-19; Adverse Events Of Special Interest,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

None.",,doi:https://doi.org/10.1016/j.eclinm.2023.101932; html:https://europepmc.org/articles/PMC10072853; pdf:https://europepmc.org/articles/PMC10072853?pdf=render 33617936,https://doi.org/10.1016/j.jhin.2021.02.012,Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.,"McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.",,The Journal of hospital infection,2021,2021-02-20,Y,,,,,,doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render -30928767,https://doi.org/10.1016/j.evalprogplan.2019.03.002,Understanding the factors that influence health promotion evaluation: The development and validation of the evaluation practice analysis survey.,"Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2019,2019-03-22,N,Measurement; Validity; reliability; Health Promotion; Evaluation Capacity Building; Evaluation Practice,,,"The demand for improved quality of health promotion evaluation and greater capacity to undertake evaluation is growing, yet evidence of the challenges and facilitators to evaluation practice within the health promotion field is lacking. A limited number of evaluation capacity measurement instruments have been validated in government or non-government organisations (NGO), however there is no instrument designed for health promotion organisations. This study aimed to develop and validate an Evaluation Practice Analysis Survey (EPAS) to examine evaluation practices in health promotion organisations. Qualitative interviews, existing frameworks and instruments informed the survey development. Health promotion practitioners from government agencies and NGOs completed the survey (n = 169). Principal components analysis was used to determine scale structure and Cronbach's α used to estimate internal reliability. Logistic regression was conducted to assess predictive validity of selected EPAS scale. The final survey instrument included 25 scales (125 items). The EPAS demonstrated good internal reliability (α > 0.7) for 23 scales. Dedicated resources and time for evaluation, leadership, organisational culture and internal support for evaluation showed promising predictive validity. The EPAS can be used to describe elements of evaluation capacity at the individual, organisational and system levels and to guide initiatives to improve evaluation practice in health promotion organisations.",,doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002 +37034358,https://doi.org/10.1016/j.eclinm.2023.101932,Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.,"Voss EA, Shoaibi A, Yin Hui Lai L, Blacketer C, Alshammari T, Makadia R, Haynes K, Sena AG, Rao G, van Sandijk S, Fraboulet C, Boyer L, Le Carrour T, Horban S, Morales DR, Martínez Roldán J, Ramírez-Anguita JM, Mayer MA, de Wilde M, John LH, Duarte-Salles T, Roel E, Pistillo A, Kolde R, Maljković F, Denaxas S, Papez V, Kahn MG, Natarajan K, Reich C, Secora A, Minty EP, Shah NH, Posada JD, Garcia Morales MT, Bosca D, Cadenas Juanino H, Diaz Holgado A, Pedrera Jiménez M, Serrano Balazote P, García Barrio N, Şen S, Üresin AY, Erdogan B, Belmans L, Byttebier G, Malbrain MLNG, Dedman DJ, Cuccu Z, Vashisht R, Butte AJ, Patel A, Dahm L, Han C, Bu F, Arshad F, Ostropolets A, Nyberg F, Hripcsak G, Suchard MA, Prieto-Alhambra D, Rijnbeek PR, Schuemie MJ, Ryan PB.",,EClinicalMedicine,2023,2023-04-04,Y,Observational Research; Omop Cdm; Covid-19; Adverse Events Of Special Interest,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

None.",,doi:https://doi.org/10.1016/j.eclinm.2023.101932; html:https://europepmc.org/articles/PMC10072853; pdf:https://europepmc.org/articles/PMC10072853?pdf=render 31675503,https://doi.org/10.1016/j.cell.2019.10.004,Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.,"Gurdasani D, Carstensen T, Fatumo S, Chen G, Franklin CS, Prado-Martinez J, Bouman H, Abascal F, Haber M, Tachmazidou I, Mathieson I, Ekoru K, DeGorter MK, Nsubuga RN, Finan C, Wheeler E, Chen L, Cooper DN, Schiffels S, Chen Y, Ritchie GRS, Pollard MO, Fortune MD, Mentzer AJ, Garrison E, Bergström A, Hatzikotoulas K, Adeyemo A, Doumatey A, Elding H, Wain LV, Ehret G, Auer PL, Kooperberg CL, Reiner AP, Franceschini N, Maher D, Montgomery SB, Kadie C, Widmer C, Xue Y, Seeley J, Asiki G, Kamali A, Young EH, Pomilla C, Soranzo N, Zeggini E, Pirie F, Morris AP, Heckerman D, Tyler-Smith C, Motala AA, Rotimi C, Kaleebu P, Barroso I, Sandhu MS.",,Cell,2019,2019-10-01,N,,,,"Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.",,doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004 +30928767,https://doi.org/10.1016/j.evalprogplan.2019.03.002,Understanding the factors that influence health promotion evaluation: The development and validation of the evaluation practice analysis survey.,"Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2019,2019-03-22,N,Measurement; Validity; reliability; Health Promotion; Evaluation Capacity Building; Evaluation Practice,,,"The demand for improved quality of health promotion evaluation and greater capacity to undertake evaluation is growing, yet evidence of the challenges and facilitators to evaluation practice within the health promotion field is lacking. A limited number of evaluation capacity measurement instruments have been validated in government or non-government organisations (NGO), however there is no instrument designed for health promotion organisations. This study aimed to develop and validate an Evaluation Practice Analysis Survey (EPAS) to examine evaluation practices in health promotion organisations. Qualitative interviews, existing frameworks and instruments informed the survey development. Health promotion practitioners from government agencies and NGOs completed the survey (n = 169). Principal components analysis was used to determine scale structure and Cronbach's α used to estimate internal reliability. Logistic regression was conducted to assess predictive validity of selected EPAS scale. The final survey instrument included 25 scales (125 items). The EPAS demonstrated good internal reliability (α > 0.7) for 23 scales. Dedicated resources and time for evaluation, leadership, organisational culture and internal support for evaluation showed promising predictive validity. The EPAS can be used to describe elements of evaluation capacity at the individual, organisational and system levels and to guide initiatives to improve evaluation practice in health promotion organisations.",,doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002 34172543,https://doi.org/10.1136/bmjopen-2020-042893,Developing a model to predict individualised treatment for gonorrhoea: a modelling study.,"Findlater L, Mohammed H, Gobin M, Fifer H, Ross J, Geffen Obregon O, Turner KME.",,BMJ open,2021,2021-06-25,Y,epidemiology; Public Health; Genitourinary Medicine; Sexual Medicine,,,"

Objective

To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone.

Design

A modelling study.

Setting

England and Wales.

Participants

Individuals accessing sentinel health services.

Intervention

Developing an Excel model which uses participants' demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015-2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme.

Main outcome measures

Estimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation.

Results

Between 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%-51%) and penicillin (range: 6%-33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment.

Conclusions

Using demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.",,doi:https://doi.org/10.1136/bmjopen-2020-042893; html:https://europepmc.org/articles/PMC8237724; pdf:https://europepmc.org/articles/PMC8237724?pdf=render 32430455,https://doi.org/10.1136/bmjopen-2020-038530,Evaluating the real-world implementation of the Family Nurse Partnership in England: protocol for a data linkage study.,"Cavallaro FL, Gilbert R, Wijlaars L, Kennedy E, Swarbrick A, van der Meulen J, Harron K.",,BMJ open,2020,2020-05-18,Y,Public Health; Community Child Health; Child Protection; Health Informatics,,,"

Introduction

Almost 20 000 babies are born to teenage mothers each year in England, with poorer outcomes for mothers and babies than among older mothers. A nurse home visitation programme in the USA was found to improve a wide range of outcomes for young mothers and their children. However, a randomised controlled trial in England found no effect on short-term primary outcomes, although cognitive development up to age 2 showed improvement. Our study will use linked routinely collected health, education and social care data to evaluate the real-world effects of the Family Nurse Partnership (FNP) on child outcomes up to age 7, with a focus on identifying whether the FNP works better for particular groups of families, thereby informing programme targeting and resource allocation.

Methods and analysis

We will construct a retrospective cohort of all women aged 13-24 years giving birth in English NHS hospitals between 2010 and 2017, linking information on mothers and children from FNP programme data, Hospital Episodes Statistics and the National Pupil Database. To assess the effectiveness of FNP, we will compare outcomes for eligible mothers ever and never enrolled in FNP, and their children, using two analysis strategies to adjust for measured confounding: propensity score matching and analyses adjusting for maternal characteristics up to enrolment/28 weeks gestation. Outcomes of interest include early childhood development, childhood unplanned hospital admissions for injury or maltreatment-related diagnoses and children in care. Subgroup analyses will determine whether the effect of FNP varied according to maternal characteristics (eg, age and education).

Ethics and dissemination

The Nottingham Research Ethics Committee approved this study. Mothers participating in FNP were supportive of our planned research. Results will inform policy-makers for targeting home visiting programmes. Methodological findings on the accuracy and reliability of cross-sectoral data linkage will be of interest to researchers.",,doi:https://doi.org/10.1136/bmjopen-2020-038530; html:https://europepmc.org/articles/PMC7239518; pdf:https://europepmc.org/articles/PMC7239518?pdf=render 34468322,https://doi.org/10.2196/30083,An Early Warning Risk Prediction Tool (RECAP-V1) for Patients Diagnosed With COVID-19: Protocol for a Statistical Analysis Plan.,"Fiorentino F, Prociuk D, Espinosa Gonzalez AB, Neves AL, Husain L, Ramtale SC, Mi E, Mi E, Macartney J, Anand SN, Sherlock J, Saravanakumar K, Mayer E, de Lusignan S, Greenhalgh T, Delaney BC.",,JMIR research protocols,2021,2021-10-05,Y,Modeling; Early warning; Risk Score; Remote Assessment; Covid-19,,,"

Background

Since the start of the COVID-19 pandemic, efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalization. The RECAP (Remote COVID-19 Assessment in Primary Care) study investigates the predictive risk of hospitalization, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process performed by clinicians. We aim to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of several general practices across the United Kingdom to construct accurate predictive models. The models will be based on preexisting conditions and monitoring data of a patient's clinical parameters (eg, blood oxygen saturation) to make reliable predictions as to the patient's risk of hospital admission, deterioration, and death.

Objective

This statistical analysis plan outlines the statistical methods to build the prediction model to be used in the prioritization of patients in the primary care setting. The statistical analysis plan for the RECAP study includes the development and validation of the RECAP-V1 prediction model as a primary outcome. This prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected COVID-19. The model will predict the risk of deterioration and hospitalization.

Methods

After the data have been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine-learning approaches to impute the missing data for the final analysis. For predictive model development, we will use multiple logistic regression analyses to construct the model. We aim to recruit a minimum of 1317 patients for model development and validation. We will then externally validate the model on an independent dataset of 1400 patients. The model will also be applied for multiple different datasets to assess both its performance in different patient groups and its applicability for different methods of data collection.

Results

As of May 10, 2021, we have recruited 3732 patients. A further 2088 patients have been recruited through the National Health Service Clinical Assessment Service, and approximately 5000 patients have been recruited through the DoctalyHealth platform.

Conclusions

The methodology for the development of the RECAP-V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritize COVID-19 patients.

Trial registration

ClinicalTrials.gov NCT04435041; https://clinicaltrials.gov/ct2/show/NCT04435041.

International registered report identifier (irrid)

DERR1-10.2196/30083.",,doi:https://doi.org/10.2196/30083; html:https://europepmc.org/articles/PMC8494068 -35231023,https://doi.org/10.1371/journal.pmed.1003907,Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.,"Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.",,PLoS medicine,2022,2022-03-01,Y,,,,"

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.",,doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render 33004356,https://doi.org/10.3399/bjgp20x712673,First do no harm: valproate and medicines safety in pregnancy.,"Robson J, Moss N, McGettigan P, Beardsley SJ, Lovegrove E, Dezateux C.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2020,2020-10-01,N,,,,,,doi:https://doi.org/10.3399/bjgp20X712673; html:https://europepmc.org/articles/PMC7518898; pdf:https://europepmc.org/articles/PMC7518898?pdf=render; doi:https://doi.org/10.3399/bjgp20x712673 +35231023,https://doi.org/10.1371/journal.pmed.1003907,Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.,"Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.",,PLoS medicine,2022,2022-03-01,Y,,,,"

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.",,doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render 34600625,https://doi.org/10.1016/s0140-6736(21)01609-3,"Fatal police violence by race and state in the USA, 1980-2019: a network meta-regression.",GBD 2019 Police Violence US Subnational Collaborators.,,"Lancet (London, England)",2021,2021-10-01,Y,,,,"

Background

The burden of fatal police violence is an urgent public health crisis in the USA. Mounting evidence shows that deaths at the hands of the police disproportionately impact people of certain races and ethnicities, pointing to systemic racism in policing. Recent high-profile killings by police in the USA have prompted calls for more extensive and public data reporting on police violence. This study examines the presence and extent of under-reporting of police violence in US Government-run vital registration data, offers a method for correcting under-reporting in these datasets, and presents revised estimates of deaths due to police violence in the USA.

Methods

We compared data from the USA National Vital Statistics System (NVSS) to three non-governmental, open-source databases on police violence: Fatal Encounters, Mapping Police Violence, and The Counted. We extracted and standardised the age, sex, US state of death registration, year of death, and race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic of other races, and Hispanic of any race) of each decedent for all data sources and used a network meta-regression to quantify the rate of under-reporting within the NVSS. Using these rates to inform correction factors, we provide adjusted estimates of deaths due to police violence for all states, ages, sexes, and racial and ethnic groups from 1980 to 2019 across the USA.

Findings

Across all races and states in the USA, we estimate 30 800 deaths (95% uncertainty interval [UI] 30 300-31 300) from police violence between 1980 and 2018; this represents 17 100 more deaths (16 600-17 600) than reported by the NVSS. Over this time period, the age-standardised mortality rate due to police violence was highest in non-Hispanic Black people (0·69 [95% UI 0·67-0·71] per 100 000), followed by Hispanic people of any race (0·35 [0·34-0·36]), non-Hispanic White people (0·20 [0·19-0·20]), and non-Hispanic people of other races (0·15 [0·14- 0·16]). This variation is further affected by the decedent's sex and shows large discrepancies between states. Between 1980 and 2018, the NVSS did not report 55·5% (54·8-56·2) of all deaths attributable to police violence. When aggregating all races, the age-standardised mortality rate due to police violence was 0·25 (0·24-0·26) per 100 000 in the 1980s and 0·34 (0·34-0·35) per 100 000 in the 2010s, an increase of 38·4% (32·4-45·1) over the period of study.

Interpretation

We found that more than half of all deaths due to police violence that we estimated in the USA from 1980 to 2018 were unreported in the NVSS. Compounding this, we found substantial differences in the age-standardised mortality rate due to police violence over time and by racial and ethnic groups within the USA. Proven public health intervention strategies are needed to address these systematic biases. State-level estimates allow for appropriate targeting of these strategies to address police violence and improve its reporting.

Funding

Bill & Melinda Gates Foundation, National Institute on Minority Health and Health Disparities, and National Heart, Lung, and Blood Institute.",,doi:https://doi.org/10.1016/S0140-6736(21)01609-3; html:https://europepmc.org/articles/PMC8485022; pdf:https://europepmc.org/articles/PMC8485022?pdf=render 33714592,https://doi.org/10.1016/j.mayocp.2021.02.007,"Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.","Wu J, Mafham M, Mamas MA, Rashid M, Kontopantelis E, Deanfield JE, de Belder MA, Gale CP.",,Mayo Clinic proceedings,2021,2021-02-16,Y,,,,"

Objective

To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.

Methods

This national death registry included all adult (aged ≥18 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.

Results

Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.

Conclusion

The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.",,doi:https://doi.org/10.1016/j.mayocp.2021.02.007; html:https://europepmc.org/articles/PMC7885692; pdf:https://europepmc.org/articles/PMC7885692?pdf=render 31504409,https://doi.org/10.1093/eurheartj/ehz587,The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.,"Van't Klooster CC, Ridker PM, Hjortnaes J, van der Graaf Y, Asselbergs FW, Westerink J, Aerts JGJV, Visseren FLJ.",,European heart journal,2019,2019-12-01,Y,Risk factor; High-sensitive C-reactive Protein; Incident Cancer; Chronic Systemic Low-grade Inflammation; Patients With Vascular Disease,,,"

Aims

Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD.

Methods and results

In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05).

Conclusion

Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.","Inflammation is a risk factor for cardiovascular disease (CVD) and is linked with a higher risk of cancer. This study investigates the relationship between inflammation and risk of cancer in patients with stable CVD. The study reports that low-grade inflammation, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD.",doi:https://doi.org/10.1093/eurheartj/ehz587; html:https://europepmc.org/articles/PMC6925382; pdf:https://europepmc.org/articles/PMC6925382?pdf=render @@ -1822,19 +1824,19 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34515361,https://doi.org/10.15252/embj.2021108610,Porin threading drives receptor disengagement and establishes active colicin transport through Escherichia coli OmpF.,"Francis MR, Webby MN, Housden NG, Kaminska R, Elliston E, Chinthammit B, Lukoyanova N, Kleanthous C.",,The EMBO journal,2021,2021-09-13,Y,Cryo-electron microscopy; Outer membrane; Bacteriocins; Gram-negative Bacteria; fluorescent microscopy,,,"Bacteria deploy weapons to kill their neighbours during competition for resources and to aid survival within microbiomes. Colicins were the first such antibacterial system identified, yet how these bacteriocins cross the outer membrane (OM) of Escherichia coli is unknown. Here, by solving the structures of translocation intermediates via cryo-EM and by imaging toxin import, we uncover the mechanism by which the Tol-dependent nuclease colicin E9 (ColE9) crosses the bacterial OM. We show that threading of ColE9's disordered N-terminal domain through two pores of the trimeric porin OmpF causes the colicin to disengage from its primary receptor, BtuB, and reorganises the translocon either side of the membrane. Subsequent import of ColE9 through the lumen of a single OmpF subunit is driven by the proton-motive force, which is delivered by the TolQ-TolR-TolA-TolB assembly. Our study answers longstanding questions, such as why OmpF is a better translocator than OmpC, and reconciles the mechanisms by which both Tol- and Ton-dependent bacteriocins cross the bacterial outer membrane.",,doi:https://doi.org/10.15252/embj.2021108610; html:https://europepmc.org/articles/PMC8561637; pdf:https://europepmc.org/articles/PMC8561637?pdf=render 31062032,https://doi.org/10.1093/ije/dyz073,"Cohort Profile: Extended Cohort for E-health, Environment and DNA (EXCEED).","John C, Reeve NF, Free RC, Williams AT, Ntalla I, Farmaki AE, Bethea J, Barton LM, Shrine N, Batini C, Packer R, Terry S, Hargadon B, Wang Q, Melbourne CA, Adams EL, Bee CE, Harrington K, Miola J, Brunskill NJ, Brightling CE, Barwell J, Wallace SE, Hsu R, Shepherd DJ, Hollox EJ, Wain LV, Tobin MD.",,International journal of epidemiology,2019,2019-06-01,Y,,,,,,doi:https://doi.org/10.1093/ije/dyz073; html:https://europepmc.org/articles/PMC6659362; pdf:https://europepmc.org/articles/PMC6659362?pdf=render 32934998,https://doi.org/10.23889/ijpds.v3i1.412,Creating individual level air pollution exposures in an anonymised data safe haven: a platform for evaluating impact on educational attainment.,"Mizen A, Lyons J, Doherty R, Berridge D, Wilkinson P, Milojevic A, Carruthers D, Akbari A, Lake I, Davies GA, Sallakh MA, Mavrogianni A, Dearden L, Johnson R, Rodgers SE.",,International journal of population data science,2018,2018-08-21,Y,Air pollution; Cognition; Asthma; Data Linkage; Seasonal Allergic Rhinitis,,,"

Introduction

There is a lack of evidence on the adverse effects of air pollution on cognition for people with air quality-related health conditions. We propose that educational attainment, as a proxy for cognition, may increase with improved air quality. This study will explore whether asthma and seasonal allergic rhinitis, when exacerbated by acute exposure to air pollution, is associated with educational attainment.

Objective

To describe the preparation of individual and household-level linked environmental and health data for analysis within an anonymised safe haven. Also to introduce our statistical analysis plan for our study: COgnition, Respiratory Tract illness and Effects of eXposure (CORTEX).

Methods

We imported daily air pollution and aeroallergen data, and individual level education data into the SAIL databank, an anonymised safe haven for person-based records. We linked individual-level education, socioeconomic and health data to air quality data for home and school locations, creating tailored exposures for individuals across a city. We developed daily exposure data for all pupils in repeated cross sectional exam cohorts (2009-2015).

Conclusion

We have used the SAIL databank, an innovative, data safe haven to create individual-level exposures to air pollution and pollen for multiple daily home and school locations. The analysis platform will allow us to evaluate retrospectively the impact of air quality on attainment for multiple cross-sectional cohorts of pupils. Our methods will allow us to distinguish between the pollution impacts on educational attainment for pupils with and without respiratory health conditions. The results from this study will further our understanding of the effects of air quality and respiratory-related health conditions on cognition.

Highlights

This city-wide study includes longitudinal routinely-recorded educational attainment data for all pupils taking exams over seven years;High spatial resolution air pollution data were linked within a privacy protected databank to obtain individual exposure at multiple daily locations;This study will use health data linked at the individual level to explore associations between air pollution, related morbidity, and educational attainment.",,doi:https://doi.org/10.23889/ijpds.v3i1.412; html:https://europepmc.org/articles/PMC7299475; pdf:https://europepmc.org/articles/PMC7299475?pdf=render -33628949,https://doi.org/10.12688/wellcomeopenres.16020.1,The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020. ,"Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.",,Wellcome open research,2020,2020-06-10,Y,,,,"The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across the parent and offspring generations between the 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 partners of offspring). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases fell between 1.03% - 4.19% depending on timing of measurement during the period of reporting. Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.",,doi:https://doi.org/10.12688/wellcomeopenres.16020.1; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render 31787481,https://doi.org/10.1016/j.schres.2019.10.061,Association of physical health multimorbidity with mortality in people with schizophrenia spectrum disorders: Using a novel semantic search system that captures physical diseases in electronic patient records.,"Kugathasan P, Wu H, Gaughran F, Nielsen RE, Pritchard M, Dobson R, Stewart R, Stubbs B.",,Schizophrenia research,2020,2019-11-28,N,Mortality; Schizophrenia; Somatic; Comorbidity; Severe Mental Illness,,,"

Objective

Single physical comorbidities have been associated with the premature mortality in people with schizophrenia-spectrum disorders (SSD). We investigated the association of physical multimorbidity (≥two physical health conditions) with mortality in people with SSD.

Methods

A retrospective cohort study between 2013 and 2017. All people with a diagnosis of SSD (ICD-10: F20-F29), who had contact with secondary mental healthcare within South London during 2011-2012 were included. A novel semantic search system captured conditions from electronic mental health records, and all-cause mortality were retrieved. Hazard ratios (HRs) and population attributable fractions (PAFs) were calculated for associations between physical multimorbidity and all-cause mortality.

Results

Among the 9775 people with SSD (mean (SD) age, 45.9 (15.4); males, 59.3%), 6262 (64%) had physical multimorbidity, and 880 (9%) died during the 5-year follow-up. The top three physical multimorbidity combinations with highest mortality were cardiovascular-respiratory (HR: 2.23; 95% CI, 1.49-3.32), respiratory-skin (HR: 2.06; 95% CI, 1.31-3.24), and respiratory-digestive (HR: 1.88; 95% CI, 1.14-3.11), when adjusted for age, gender, and all other physical disease systems. Combinations of physical diseases with highest PAFs were cardiovascular-respiratory (PAF: 35.7%), neurologic-respiratory (PAF: 32.7%), as well as respiratory-skin (PAF: 29.8%).

Conclusions

Approximately 2/3 of patients with SSD had physical multimorbidity and the risk of mortality in these patients was further increased compared to those with none or single physical conditions. These findings suggest that in order to reduce the physical health burden and subsequent mortality in people with SSD, proactive coordinated prevention and management efforts are required and should extend beyond the current focus on single physical comorbidities.",,doi:https://doi.org/10.1016/j.schres.2019.10.061 32987048,https://doi.org/10.1016/j.ijcard.2020.09.053,Predicting 10-year risk of recurrent cardiovascular events andcardiovascular interventions in patients with established cardiovascular disease: results from UCC-SMART and REACH.,"Klooster CCV', Bhatt DL, Steg PG, Massaro JM, Dorresteijn JAN, Westerink J, Ruigrok YM, de Borst GJ, Asselbergs FW, van der Graaf Y, Visseren FLJ, UCC-SMART study group.",,International journal of cardiology,2021,2020-09-25,N,Risk Prediction; Cardiovascular Interventions; Major Cardiovascular Events; Patients With Established Cardiovascular Disease,,,"

Background

Existing cardiovascular risk scores for patients with established cardiovascular disease (CVD) estimate residual risk of recurrent major cardiovascular events (MACE). The aim of the current study is to develop and externally validate a prediction model to estimate the 10-year combined risk of recurrent MACE and cardiovascular interventions (MACE+) in patients with established CVD.

Methods

Data of patients with established CVD from the UCC-SMART cohort (N = 8421) were used for model development, and patient data from REACH Western Europe (N = 14,528) and REACH North America (N = 19,495) for model validation. Predictors were selected based on the existing SMART risk score. A Fine and Gray competing risk-adjusted 10-year risk model was developed for the combined outcome MACE+. The model was validated in all patients and in strata of coronary heart disease (CHD), cerebrovascular disease (CeVD), peripheral artery disease (PAD).

Results

External calibration for 2-year risk in REACH Western Europe and REACH North America was good, c-statistics were moderate: 0.60 and 0.58, respectively. In strata of CVD at baseline good external calibration was observed in patients with CHD and CeVD, however, poor calibration was seen in patients with PAD. C-statistics for patients with CHD were 0.60 and 0.57, for patients with CeVD 0.62 and 0.61, and for patients with PAD 0.53 and 0.54 in REACH Western Europe and REACH North America, respectively.

Conclusions

The 10-year combined risk of recurrent MACE and cardiovascular interventions can be estimated in patients with established CHD or CeVD. However, cardiovascular interventions in patients with PAD could not be predicted reliably.",,doi:https://doi.org/10.1016/j.ijcard.2020.09.053 35235826,https://doi.org/10.1016/j.ijid.2022.02.051,"Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections - a survival analysis.","Hussey H, Davies MA, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Wasserman S, Boloko L, Symons G, Raubenheimer P, Parker A, Schrueder N, Solomon W, Rousseau P, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Boulle A, Hsiao NY.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2022,2022-02-27,Y,South Africa; Clinical Severity; Sars-cov-2; Omicron Variant; Rdrp Target Delay,,,"

Background

At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity.

Methods

RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection.

Results

A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.",,doi:https://doi.org/10.1016/j.ijid.2022.02.051; html:https://europepmc.org/articles/PMC8882068; pdf:https://europepmc.org/articles/PMC8882068?pdf=render 35300523,https://doi.org/10.1161/circulationaha.121.056663,Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization.,"Henry A, Gordillo-Marañón M, Finan C, Schmidt AF, Ferreira JP, Karra R, Sundström J, Lind L, Ärnlöv J, Zannad F, Mälarstig A, Hingorani AD, Lumbers RT, HERMES and SCALLOP Consortia.",,Circulation,2022,2022-03-18,Y,Proteomics; Heart Failure; Drug Target Prediction; Mendelian Randomization Analysis,,,"

Background

Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets.

Methods

We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using cis-protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 individuals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis.

Results

Forty-four of ninety proteins were positively associated with risk of incident HF (P<6.0×10-4). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1.

Conclusions

We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.",,doi:https://doi.org/10.1161/CIRCULATIONAHA.121.056663; html:https://europepmc.org/articles/PMC9010023; pdf:https://europepmc.org/articles/PMC9010023?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056663 32360702,https://doi.org/10.1016/j.ijcard.2020.04.068,Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.,"Savarese G, Settergren C, Schrage B, Thorvaldsen T, Löfman I, Sartipy U, Mellbin L, Meyers A, Farsani SF, Brueckmann M, Brodovicz KG, Vedin O, Asselbergs FW, Dahlström U, Cosentino F, Lund LH.",,International journal of cardiology,2020,2020-04-30,N,Type 2 diabetes mellitus; Atrial fibrillation; Ejection fraction; Heart Failure; Chronic Kidney Disease; Trial Design,,,"

Background

Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.

Methods and results

Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.

Conclusion

HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.",,doi:https://doi.org/10.1016/j.ijcard.2020.04.068 +33628949,https://doi.org/10.12688/wellcomeopenres.16020.1,The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020. ,"Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.",,Wellcome open research,2020,2020-06-10,Y,,,,"The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across the parent and offspring generations between the 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 partners of offspring). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases fell between 1.03% - 4.19% depending on timing of measurement during the period of reporting. Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.",,doi:https://doi.org/10.12688/wellcomeopenres.16020.1; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render 31196905,https://doi.org/10.1136/bmjopen-2019-028929,Recorded poor insight as a predictor of service use outcomes: cohort study of patients with first-episode psychosis in a large mental healthcare database.,"Ramu N, Kolliakou A, Sanyal J, Patel R, Stewart R.",,BMJ open,2019,2019-06-12,Y,Insight; Psychosis; Natural Language Processing; Mental Health Outcomes; Cris; Service Use Outcomes,Applied Analytics,,"

Objectives

To investigate recorded poor insight in relation to mental health and service use outcomes in a cohort with first-episode psychosis.

Design

We developed a natural language processing algorithm to ascertain statements of poor or diminished insight and tested this in a cohort of patients with first-episode psychosis.

Setting

The clinical record text at the South London and Maudsley National Health Service Trust in the UK was used.

Participants

We applied the algorithm to characterise a cohort of 2026 patients with first-episode psychosis attending an early intervention service.

Primary and secondary outcome measures

Recorded poor insight within 1 month of registration was investigated in relation to (1) incidence of psychiatric hospitalisation, (2) odds of legally enforced hospitalisation, (3) number of days spent as a mental health inpatient and (4) number of different antipsychotic agents prescribed; outcomes were measured over varying follow-up periods from 12 months to 60 months, adjusting for a range of sociodemographic and clinical covariates.

Results

Recorded poor insight, present in 48.9% of the sample, was positively associated with youngest and oldest age groups, unemployment and schizophrenia (compared with bipolar disorder) and was negatively associated with Asian ethnicity, married status, home ownership and recorded cannabis use. It was significantly associated with higher levels of all four outcomes over the succeeding 12 months. Associations with hospitalisation incidence and number of antipsychotics remained independently significant when measured over 60 and 48 months, respectively.

Conclusions

Recorded poor insight in people with recent onset psychosis predicted higher subsequent inpatient mental healthcare use. Improving insight might benefit patients' course of illness as well as reduce mental health service use.",,doi:https://doi.org/10.1136/bmjopen-2019-028929; html:https://europepmc.org/articles/PMC6577359; pdf:https://europepmc.org/articles/PMC6577359?pdf=render -37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render 33430602,https://doi.org/10.1161/circheartfailure.120.007022,Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.,"Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",,Circulation. Heart failure,2021,2021-01-12,Y,Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies,,,"

Background

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.

Methods

A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings.

Results

In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCMSMP than in HCMSMN and controls. Higher tubulin detyrosination was also found in 2 unrelated MYBPC3 mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.

Conclusions

Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCMSMP. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCMSMP, whereas a beneficial effect may be limited in patients with HCMSMN.",,doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render +37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render 32814899,https://doi.org/10.1038/s41586-020-2635-8,Genetic and functional insights into the fractal structure of the heart.,"Meyer HV, Dawes TJW, Serrani M, Bai W, Tokarczuk P, Cai J, de Marvao A, Henry A, Lumbers RT, Gierten J, Thumberger T, Wittbrodt J, Ware JS, Rueckert D, Matthews PM, Prasad SK, Costantino ML, Cook SA, Birney E, O'Regan DP.",,Nature,2020,2020-08-19,N,,,,"The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a remnant of embryonic development1,2. The function of these trabeculae in adults and their genetic architecture are unknown. Here we performed a genome-wide association study to investigate image-derived phenotypes of trabeculae using the fractal analysis of trabecular morphology in 18,096 participants of the UK Biobank. We identified 16 significant loci that contain genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborization3,4. Using biomechanical simulations and observational data from human participants, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomization, we find a causal relationship between trabecular morphology and risk of cardiovascular disease. These findings suggest a previously unknown role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity and reveal the influence of the myocardial trabeculae on susceptibility to cardiovascular disease.",,doi:https://doi.org/10.1038/s41586-020-2635-8; html:https://europepmc.org/articles/PMC7116759; pdf:https://europepmc.org/articles/PMC7116759?pdf=render; doi:https://doi.org/10.1038/s41586-020-2635-8; pdf:https://discovery.ucl.ac.uk/10110799/1/Meyer_accepted_version.pdf 35487729,https://doi.org/10.1136/bmjopen-2021-056541,"Associations of presenting symptoms and subsequent adverse clinical outcomes in people with unipolar depression: a prospective natural language processing (NLP), transdiagnostic, network analysis of electronic health record (EHR) data.","Patel R, Irving J, Brinn A, Taylor M, Shetty H, Pritchard M, Stewart R, Fusar-Poli P, McGuire P.",,BMJ open,2022,2022-04-29,Y,epidemiology; Health Informatics; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Objective

To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression.

Design

A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical outcomes.

Setting

The South London and Maudsley Clinical Record Interactive Search database.

Participants

All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018.

Exposure

(1) Symptoms of mania: Elation; Grandiosity; Flight of ideas; Irritability; Pressured speech. (2) Symptoms of depression: Disturbed mood; Anhedonia; Guilt; Hopelessness; Helplessness; Worthlessness; Tearfulness; Low energy; Reduced appetite; Weight loss. (3) Symptoms of mania or depression (overlapping symptoms): Poor concentration; Insomnia; Disturbed sleep; Agitation; Mood instability.

Main outcomes

(1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission.

Results

Out of 19 707 patients, at least 1 depression, overlapping or mania symptom was present in 18 998 (96.4%), 15 954 (81.0%) and 4671 (23.7%) patients, respectively. 2772 (14.1%) patients subsequently developed bipolar or psychotic disorder during the follow-up period. The presence of at least one mania (HR 2.00, 95% CI 1.85 to 2.16), overlapping symptom (HR 1.71, 95% CI 1.52 to 1.92) or symptom of depression (HR 1.31, 95% CI 1.07 to 1.61) were associated with significantly increased risk of onset of a bipolar or psychotic disorder. Mania (HR 1.95, 95% CI 1.77 to 2.15) and overlapping symptoms (HR 1.76, 95% CI 1.52 to 2.04) were associated with greater risk for psychiatric hospital admission than symptoms of depression (HR 1.41, 95% CI 1.06 to 1.88).

Conclusions

The presence of mania or overlapping symptoms in people with unipolar depression is associated with worse clinical outcomes. Symptom-based approaches to defining clinical phenotype may facilitate a more personalised treatment approach and better predict subsequent clinical outcomes than psychiatric diagnosis alone.",,doi:https://doi.org/10.1136/bmjopen-2021-056541; html:https://europepmc.org/articles/PMC9058769; pdf:https://europepmc.org/articles/PMC9058769?pdf=render -37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 33777379,https://doi.org/10.1093/ckj/sfaa045,Accelerometer-measured physical activity and functional behaviours among people on dialysis.,"Nawab KA, Storey BC, Staplin N, Walmsley R, Haynes R, Sutherland S, Crosbie S, Pugh CW, Harper CHS, Landray MJ, Doherty A, Herrington WG.",,Clinical kidney journal,2021,2020-08-31,Y,Age; Haemodialysis; epidemiology; Physical Activity; cardiovascular,,,"

Background

The feasibility of wrist-worn accelerometers, and the patterns and determinants of physical activity, among people on dialysis are uncertain.

Methods

People on maintenance dialysis were fitted with a wrist-worn AxivityAX3 accelerometer. Subsets also wore a 14-day electrocardiograph patch (Zio®PatchXT) and wearable cameras. Age-, sex- and season-matched UK Biobank control groups were derived for comparison.

Results

Median (interquartile range) accelerometer wear time for the 101 recruits was 12.5 (10.4-13.5) days, of which 73 participants (mean age 66.5 years) had excellent wear on both dialysis and non-dialysis days. Mean (standard error) overall physical activity levels were 15.5 (0.7) milligravity units (mg), 14.8 (0.7) mg on dialysis days versus 16.2 (0.8) mg on non-dialysis days. This compared with 28.1 (0.5) mg for apparently healthy controls, 23.4 (0.4) mg for controls with prior cardiovascular disease (CVD) and/or diabetes mellitus and 22.9 (0.6) mg for heart failure controls. Each day, we estimated that those on dialysis spent an average of about 1 hour (h/day) walking, 0.6 h/day engaging in moderate-intensity activity, 0.7 h/day on light tasks, 13.2 h/day sedentary and 8.6 h/day asleep. Older age and self-reported leg weakness were associated with decreased levels of physical activity, but the presence of prior CVD, arrhythmias and listing for transplantation were not.

Conclusions

Wrist-worn accelerometers are an acceptable and reliable method to measure physical activity in people on dialysis and may also be used to estimate functional behaviours. Among people on dialysis, who are broadly half as active as general population controls, age and leg weakness appear to be more important determinants of low activity levels than CVD.",,doi:https://doi.org/10.1093/ckj/sfaa045; html:https://europepmc.org/articles/PMC7986362; pdf:https://europepmc.org/articles/PMC7986362?pdf=render +37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 34568827,https://doi.org/10.1093/schizbullopen/sgab041,Development and Validation of a Nonremission Risk Prediction Model in First-Episode Psychosis: An Analysis of 2 Longitudinal Studies.,"Leighton SP, Krishnadas R, Upthegrove R, Marwaha S, Steyerberg EW, Gkoutos GV, Broome MR, Liddle PF, Everard L, Singh SP, Freemantle N, Fowler D, Jones PB, Sharma V, Murray R, Wykes T, Drake RJ, Buchan I, Rogers S, Cavanagh J, Lewis SW, Birchwood M, Mallikarjun PK.",,Schizophrenia bulletin open,2021,2021-01-01,Y,Schizophrenia; Prognosis; Logistic regression; early intervention; Psychotic Disorders; Precision Medicine,,,"Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.71, 0.75) and adequate calibration with intercept alpha of 0.12 (0.02, 0.22) and slope beta of 0.98 (0.85, 1.11). Our model improved the net-benefit by 15% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 15 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact.",,doi:https://doi.org/10.1093/schizbullopen/sgab041; html:https://europepmc.org/articles/PMC8458108; pdf:https://europepmc.org/articles/PMC8458108?pdf=render 34411511,https://doi.org/10.1016/s2213-2600(21)00164-8,"Global, regional, and national burden of respiratory tract cancers and associated risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.",GBD 2019 Respiratory Tract Cancers Collaborators.,,The Lancet. Respiratory medicine,2021,2021-08-16,Y,,,,"

Background

Prevention, control, and treatment of respiratory tract cancers are important steps towards achieving target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality due to non-communicable diseases by 2030. We aimed to provide global, regional, and national estimates of the burden of tracheal, bronchus, and lung cancer and larynx cancer and their attributable risks from 1990 to 2019.

Methods

Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 methodology, we evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) of respiratory tract cancers (ie, tracheal, bronchus, and lung cancer and larynx cancer). Deaths from tracheal, bronchus, and lung cancer and larynx cancer attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and the theoretical minimum risk exposure level input from 204 countries and territories, stratified by sex and Socio-demographic Index (SDI). Trends were estimated from 1990 to 2019, with an emphasis on the 2010-19 period.

Findings

Globally, there were 2·26 million (95% uncertainty interval 2·07 to 2·45) new cases of tracheal, bronchus, and lung cancer, and 2·04 million (1·88 to 2·19) deaths and 45·9 million (42·3 to 49·3) DALYs due to tracheal, bronchus, and lung cancer in 2019. There were 209 000 (194 000 to 225 000) new cases of larynx cancer, and 123 000 (115 000 to 133 000) deaths and 3·26 million (3·03 to 3·51) DALYs due to larynx cancer globally in 2019. From 2010 to 2019, the number of new tracheal, bronchus, and lung cancer cases increased by 23·3% (12·9 to 33·6) globally and the number of larynx cancer cases increased by 24·7% (16·0 to 34·1) globally. Global age-standardised incidence rates of tracheal, bronchus, and lung cancer decreased by 7·4% (-16·8 to 1·6) and age-standardised incidence rates of larynx cancer decreased by 3·0% (-10·5 to 5·0) in males over the past decade; however, during the same period, age-standardised incidence rates in females increased by 0·9% (-8·2 to 10·2) for tracheal, bronchus, and lung cancer and decreased by 0·5% (-8·4 to 8·1) for larynx cancer. Furthermore, although age-standardised incidence and death rates declined in both sexes combined from 2010 to 2019 at the global level for tracheal, bronchus, lung and larynx cancers, some locations had rising rates, particularly those on the lower end of the SDI range. Smoking contributed to an estimated 64·2% (61·9-66·4) of all deaths from tracheal, bronchus, and lung cancer and 63·4% (56·3-69·3) of all deaths from larynx cancer in 2019. For males and for both sexes combined, smoking was the leading specific risk factor for age-standardised deaths from tracheal, bronchus, and lung cancer per 100 000 in all SDI quintiles and GBD regions in 2019. However, among females, household air pollution from solid fuels was the leading specific risk factor in the low SDI quintile and in three GBD regions (central, eastern, and western sub-Saharan Africa) in 2019.

Interpretation

The numbers of incident cases and deaths from tracheal, bronchus, and lung cancer and larynx cancer increased globally during the past decade. Even more concerning, age-standardised incidence and death rates due to tracheal, bronchus, lung cancer and larynx cancer increased in some populations-namely, in the lower SDI quintiles and among females. Preventive measures such as smoking control interventions, air quality management programmes focused on major air pollution sources, and widespread access to clean energy should be prioritised in these settings.

Funding

Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2213-2600(21)00164-8; html:https://europepmc.org/articles/PMC8410610; pdf:http://www.thelancet.com/article/S2213260021001648/pdf 33879569,https://doi.org/10.1073/pnas.2009808118,Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer's disease.,"Lord J, Jermy B, Green R, Wong A, Xu J, Legido-Quigley C, Dobson R, Richards M, Proitsi P.",,Proceedings of the National Academy of Sciences of the United States of America,2021,2021-04-01,Y,Biomarkers; Alzheimer’s disease; Metabolomics; Causality; Mendelian Randomization,,,"There are currently no disease-modifying treatments for Alzheimer's disease (AD), and an understanding of preclinical causal biomarkers to help target disease pathogenesis in the earliest phases remains elusive. Here, we investigated whether 19 metabolites previously associated with midlife cognition-a preclinical predictor of AD-translate to later clinical risk, using Mendelian randomization (MR) to tease out AD-specific causal relationships. Summary statistics from the largest genome-wide association studies (GWASs) for AD and metabolites were used to perform bidirectional univariable MR. Bayesian model averaging (BMA) was additionally performed to address high correlation between metabolites and identify metabolite combinations that may be on the AD causal pathway. Univariable MR indicated four extra-large high-density lipoproteins (XL.HDL) on the causal pathway to AD: free cholesterol (XL.HDL.FC: 95% CI = 0.78 to 0.94), total lipids (XL.HDL.L: 95% CI = 0.80 to 0.97), phospholipids (XL.HDL.PL: 95% CI = 0.81 to 0.97), and concentration of XL.HDL particles (95% CI = 0.79 to 0.96), significant at an adjusted P < 0.009. MR-BMA corroborated XL.HDL.FC to be among the top three causal metabolites, in addition to total cholesterol in XL.HDL (XL.HDL.C) and glycoprotein acetyls (GP). Both XL.HDL.C and GP demonstrated suggestive univariable evidence of causality (P < 0.05), and GP successfully replicated within an independent dataset. This study offers insight into the causal relationship between metabolites demonstrating association with midlife cognition and AD. It highlights GP in addition to several XL.HDLs-particularly XL.HDL.FC-as causal candidates warranting further investigation. As AD pathology is thought to develop decades prior to symptom onset, expanding on these findings could inform risk reduction strategies.",,doi:https://doi.org/10.1073/pnas.2009808118; html:https://europepmc.org/articles/PMC8072203; pdf:https://europepmc.org/articles/PMC8072203?pdf=render @@ -1849,8 +1851,8 @@ PMC10428565,https://doi.org/,Implementation of the trial emulation approach in m 34330923,https://doi.org/10.1038/s41467-021-24930-y,Toxin import through the antibiotic efflux channel TolC.,"Housden NG, Webby MN, Lowe ED, El-Baba TJ, Kaminska R, Redfield C, Robinson CV, Kleanthous C.",,Nature communications,2021,2021-07-30,Y,,,,"Bacteria often secrete diffusible protein toxins (bacteriocins) to kill bystander cells during interbacterial competition. Here, we use biochemical, biophysical and structural analyses to show how a bacteriocin exploits TolC, a major outer-membrane antibiotic efflux channel in Gram-negative bacteria, to transport itself across the outer membrane of target cells. Klebicin C (KlebC), a rRNase toxin produced by Klebsiella pneumoniae, binds TolC of a related species (K. quasipneumoniae) with high affinity through an N-terminal, elongated helical hairpin domain common amongst bacteriocins. The KlebC helical hairpin opens like a switchblade to bind TolC. A cryo-EM structure of this partially translocated state, at 3.1 Å resolution, reveals that KlebC associates along the length of the TolC channel. Thereafter, the unstructured N-terminus of KlebC protrudes beyond the TolC iris, presenting a TonB-box sequence to the periplasm. Association with proton-motive force-linked TonB in the inner membrane drives toxin import through the channel. Finally, we demonstrate that KlebC binding to TolC blocks drug efflux from bacteria. Our results indicate that TolC, in addition to its known role in antibiotic export, can function as a protein import channel for bacteriocins.",,doi:https://doi.org/10.1038/s41467-021-24930-y; html:https://europepmc.org/articles/PMC8324772; pdf:https://europepmc.org/articles/PMC8324772?pdf=render 36434067,https://doi.org/10.1038/s42003-022-04252-5,A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.,"Bahar MW, Nasta V, Fox H, Sherry L, Grehan K, Porta C, Macadam AJ, Stonehouse NJ, Rowlands DJ, Fry EE, Stuart DI.",,Communications biology,2022,2022-11-25,Y,,,,"Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.",,doi:https://doi.org/10.1038/s42003-022-04252-5; html:https://europepmc.org/articles/PMC9700776; pdf:https://europepmc.org/articles/PMC9700776?pdf=render 32080192,https://doi.org/10.1038/s41467-020-14717-y,Author Correction: Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.,"Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M.",,Nature communications,2020,2020-02-20,Y,,,,An amendment to this paper has been published and can be accessed via a link at the top of the paper.,,doi:https://doi.org/10.1038/s41467-020-14717-y; html:https://europepmc.org/articles/PMC7033171; pdf:https://europepmc.org/articles/PMC7033171?pdf=render -36436752,https://doi.org/10.1016/j.ijid.2022.11.024,"Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2023,2022-11-24,Y,"Covid-19; Omicron; Ba.4; Death, Severe Hospitalization; Ba.5",,,"

Objectives

We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

Methods

We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.

Results

Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.

Conclusion

Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.",,doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render; doi:https://doi.org/10.1016/j.ijid.2022.11.024 32289242,https://doi.org/10.1098/rsob.190297,"Why is cancer not more common? A changing microenvironment may help to explain why, and suggests strategies for anti-cancer therapy.","Jiang X, Tomlinson IPM.",,Open biology,2020,2020-04-15,Y,Cancer Genetics; Evolutionary Biology; Mathematical Modelling,,,"One of the great unsolved puzzles in cancer biology is not why cancers occur, but rather explaining why so few cancers occur compared with the theoretical number that could occur, given the number of progenitor cells in the body and the normal mutation rate. We hypothesized that a contributory explanation is that the tumour microenvironment (TME) is not fixed due to factors such as immune cell infiltration, and that this could impair the ability of neoplastic cells to retain a high enough fitness to become a cancer. The TME has implicitly been assumed to be static in most cancer evolution models, and we therefore developed a mathematical model of spatial cancer evolution assuming that the TME, and thus the optimum cancer phenotype, changes over time. Based on simulations, we show how cancer cell populations adapt to diverse changing TME conditions and fitness landscapes. Compared with static TMEs, which generate neutral dynamics, changing TMEs lead to complex adaptations with characteristic spatio-temporal heterogeneity involving variable fitness effects of driver mutations, subclonal mixing, subclonal competition and phylogeny patterns. In many cases, cancer cell populations fail to grow or undergo spontaneous regression, and even extinction. Our analyses predict that cancer evolution in a changing TME is challenging, and can help to explain why cancer is neither inevitable nor as common as expected. Should cancer driver mutations with effects dependent of the TME exist, they are likely to be selected. Anti-cancer prevention and treatment strategies based on changing the TME are feasible and potentially effective.",,doi:https://doi.org/10.1098/rsob.190297; html:https://europepmc.org/articles/PMC7241076; pdf:https://europepmc.org/articles/PMC7241076?pdf=render +36436752,https://doi.org/10.1016/j.ijid.2022.11.024,"Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2023,2022-11-24,Y,"Covid-19; Omicron; Ba.4; Death, Severe Hospitalization; Ba.5",,,"

Objectives

We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

Methods

We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.

Results

Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.

Conclusion

Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.",,doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render; doi:https://doi.org/10.1016/j.ijid.2022.11.024 36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH). ,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 37302069,https://doi.org/10.1016/j.celrep.2023.112613,Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity.,"Potts M, Fletcher-Etherington A, Nightingale K, Mescia F, Bergamaschi L, Calero-Nieto FJ, Antrobus R, Williamson J, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Parsons H, Huttlin EL, Kingston N, Göttgens B, Bradley JR, Lehner PJ, Matheson NJ, Smith KGC, Wills MR, Lyons PA, Weekes MP.",,Cell reports,2023,2023-05-29,Y,Cp: Immunology,,,"Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. The cell-surface proteins CEACAMs1, 6, and 8, CD177, CD63, and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CEACAM1/6/8+CD177+CD63+CD89+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology.",,doi:https://doi.org/10.1016/j.celrep.2023.112613; html:https://europepmc.org/articles/PMC10243220; pdf:https://europepmc.org/articles/PMC10243220?pdf=render 34810237,https://doi.org/10.1136/thoraxjnl-2021-217629,Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol.,"Knight SR, Gupta RK, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle LCW, Openshaw PJM, Baillie JK, Docherty A, Semple MG, Noursadeghi M, Harrison EM, ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC4C) Investigators, ISARIC4C investigators.",,Thorax,2022,2021-11-22,Y,Covid-19,,,"

Purpose

To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19.

Methods

Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups.

Results

76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, -0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions.

Conclusion

Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making.

Trial registration number

ISRCTN66726260.",,doi:https://doi.org/10.1136/thoraxjnl-2021-217629; html:https://europepmc.org/articles/PMC8610617; pdf:https://europepmc.org/articles/PMC8610617?pdf=render @@ -1874,15 +1876,15 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 36527096,https://doi.org/10.1186/s12910-022-00875-9,"""Data makes the story come to life:"" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.","Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",,BMC medical ethics,2022,2022-12-16,Y,Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19,,,"The aim of UK-REACH (""The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers"") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a ""Big Data Ethics by Design"" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",,doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render 36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render 33087179,https://doi.org/10.1186/s12916-020-01790-9,Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.,"Russell TW, Golding N, Hellewell J, Abbott S, Wright L, Pearson CAB, van Zandvoort K, Jarvis CI, Gibbs H, Liu Y, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,BMC medicine,2020,2020-10-22,Y,Surveillance; Situational Awareness; Under-reporting; Case Ascertainment; Outbreak Analysis; Covid-19; Sars-cov-2,,,"

Background

Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.

Methods

Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.

Results

Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6-24%) (Belgium).

Conclusions

We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.",,doi:https://doi.org/10.1186/s12916-020-01790-9; html:https://europepmc.org/articles/PMC7577796; pdf:https://europepmc.org/articles/PMC7577796?pdf=render -35296488,https://doi.org/10.1136/bmjopen-2021-058552,"AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.","Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",,BMJ open,2022,2022-03-16,Y,Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology,,,"

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",,doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render 31862893,https://doi.org/10.1038/s41467-019-13848-1,Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.,"Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M.",,Nature communications,2019,2019-12-20,Y,,,,"Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.",,doi:https://doi.org/10.1038/s41467-019-13848-1; html:https://europepmc.org/articles/PMC6925280; pdf:https://europepmc.org/articles/PMC6925280?pdf=render -33623826,https://doi.org/10.12688/wellcomeopenres.16164.2,"The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study.","Leng T, White C, Hilton J, Kucharski A, Pellis L, Stage H, Davies NG, Centre for Mathematical Modelling of Infectious Disease 2019 nCoV Working Group, Keeling MJ, Flasche S.",,Wellcome open research,2020,2020-01-01,Y,Exit Strategy; Covid-19; Contact Clustering; Social Bubble,,,"Background: ​ During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: ​ We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. Results:  Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. Conclusions: ​ If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.",,doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render +35296488,https://doi.org/10.1136/bmjopen-2021-058552,"AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.","Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",,BMJ open,2022,2022-03-16,Y,Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology,,,"

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",,doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render +33623826,https://doi.org/10.12688/wellcomeopenres.16164.2,"The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study.","Leng T, White C, Hilton J, Kucharski A, Pellis L, Stage H, Davies NG, Centre for Mathematical Modelling of Infectious Disease 2019 nCoV Working Group, Keeling MJ, Flasche S.",,Wellcome open research,2020,2020-01-01,Y,Exit Strategy; Covid-19; Contact Clustering; Social Bubble,,,"Background: ​ During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: ​ We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. Results:  Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. Conclusions: ​ If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.",,doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render; doi:https://doi.org/10.12688/wellcomeopenres.16164.2 36269859,https://doi.org/10.1073/pnas.2206083119,Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer's disease.,"Dehghan A, Pinto RC, Karaman I, Huang J, Durainayagam BR, Ghanbari M, Nazeer A, Zhong Q, Liggi S, Whiley L, Mustafa R, Kivipelto M, Solomon A, Ngandu T, Kanekiyo T, Aikawa T, Radulescu CI, Barnes SJ, Graça G, Chekmeneva E, Camuzeaux S, Lewis MR, Kaluarachchi MR, Ikram MA, Holmes E, Tzoulaki I, Matthews PM, Griffin JL, Elliott P.",,Proceedings of the National Academy of Sciences of the United States of America,2022,2022-10-21,Y,Ceramide; Alzheimer’s disease; Metabolomics; Genome-wide Association Study; Abca7,,,"Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer's disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10-5 to 1.3 × 10-44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049-1.4 × 10-5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD.",,doi:https://doi.org/10.1073/pnas.2206083119; html:https://europepmc.org/articles/PMC9618092; pdf:https://europepmc.org/articles/PMC9618092?pdf=render; doi:https://doi.org/10.1073/pnas.2206083119 35523486,https://doi.org/10.1136/bmjopen-2021-059258,Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.,"de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.",,BMJ open,2022,2022-05-06,Y,Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders,,,"

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.",,doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render 36895957,https://doi.org/10.1093/braincomms/fcad037,Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.,"Themistocleous AC, Baskozos G, Blesneac I, Comini M, Megy K, Chong S, Deevi SVV, Ginsberg L, Gosal D, Hadden RDM, Horvath R, Mahdi-Rogers M, Manzur A, Mapeta R, Marshall A, Matthews E, McCarthy MI, Reilly MM, Renton T, Rice ASC, Vale TA, van Zuydam N, Walker SM, Woods CG, Bennett DLH.",,Brain communications,2023,2023-02-20,Y,Sodium channels; Neuropathic pain; Peripheral Neuropathy; Whole Genome Sequencing,,,"The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The TRPA1(ENST00000262209.4):c.515C>T, p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function NaV1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.",,doi:https://doi.org/10.1093/braincomms/fcad037; html:https://europepmc.org/articles/PMC9991512; pdf:https://europepmc.org/articles/PMC9991512?pdf=render 35189575,https://doi.org/10.1016/j.ebiom.2022.103878,The impact of hypoxia on B cells in COVID-19.,"Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Peñalver A, Richoz N, Moore SD, Ortmann BM, Dunmore BJ, Morgan MD, Tuong ZK, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",,EBioMedicine,2022,2022-02-19,Y,Hypoxia; B cells; Lymphopenia; Covid-19,,,"

Background

Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19.

Methods

Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice.

Findings

We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions.

Interpretation

Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes.

Funding

Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",,doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?pdf=render -37393924,https://doi.org/10.1016/s0140-6736(23)00860-7,"The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.",GBD 2019 Child and Adolescent Communicable Disease Collaborators.,,"Lancet (London, England)",2023,2023-06-29,Y,,,,"

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render 32546850,https://doi.org/10.1038/s41598-020-66737-9,Genetic aetiology of self-harm ideation and behaviour.,"Campos AI, Verweij KJH, Statham DJ, Madden PAF, Maciejewski DF, Davis KAS, John A, Hotopf M, Heath AC, Martin NG, Rentería ME.",,Scientific reports,2020,2020-06-16,Y,,,,"Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (hsnp2) estimates were ~10%, and both traits were highly genetically correlated (LDSC rg > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.",,doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render +37393924,https://doi.org/10.1016/s0140-6736(23)00860-7,"The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.",GBD 2019 Child and Adolescent Communicable Disease Collaborators.,,"Lancet (London, England)",2023,2023-06-29,Y,,,,"

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render 34321180,https://doi.org/10.1016/j.aucc.2021.05.013,The impact of distance on post-ICU disability.,"D'Arcy J, Haines K, Paul E, Doherty Z, Goodwin A, Bailey M, Barrett J, Bellomo R, Bucknall T, Gabbe BJ, Higgins AM, Iwashyna TJ, Murray LJ, Myles PS, Ponsford J, Pilcher D, Udy AA, Walker C, Young M, Cooper DJJ, Hodgson CL, ICU-Recovery Investigators.",,Australian critical care : official journal of the Confederation of Australian Critical Care Nurses,2022,2021-07-25,N,Quality of life; Mechanical ventilation; Distance; Disability; Intensive Care,,,"

Background

Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.

Objectives

The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.

Methods

This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.

Results

A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.",,doi:https://doi.org/10.1016/j.aucc.2021.05.013 32097451,https://doi.org/10.1093/ije/dyaa015,Commentary: Using human genetics to guide the repurposing of medicines.,"Bovijn J, Censin JC, Lindgren CM, Holmes MV.",,International journal of epidemiology,2020,2020-08-01,N,,,,,,doi:https://doi.org/10.1093/ije/dyaa015; html:https://europepmc.org/articles/PMC7660148; pdf:https://europepmc.org/articles/PMC7660148?pdf=render; doi:https://doi.org/10.1093/ije/dyaa015 32706893,https://doi.org/10.1182/bloodadvances.2020002230,Artificial intelligence-based morphological fingerprinting of megakaryocytes: a new tool for assessing disease in MPN patients.,"Sirinukunwattana K, Aberdeen A, Theissen H, Sousos N, Psaila B, Mead AJ, Turner GDH, Rees G, Rittscher J, Royston D.",,Blood advances,2020,2020-07-01,N,,,,"Accurate diagnosis and classification of myeloproliferative neoplasms (MPNs) requires integration of clinical, morphological, and genetic findings. Despite major advances in our understanding of the molecular and genetic basis of MPNs, the morphological assessment of bone marrow trephines (BMT) is critical in differentiating MPN subtypes and their reactive mimics. However, morphological assessment is heavily constrained by a reliance on subjective, qualitative, and poorly reproducible criteria. To improve the morphological assessment of MPNs, we have developed a machine learning approach for the automated identification, quantitative analysis, and abstract representation of megakaryocyte features using reactive/nonneoplastic BMT samples (n = 43) and those from patients with established diagnoses of essential thrombocythemia (n = 45), polycythemia vera (n = 18), or myelofibrosis (n = 25). We describe the application of an automated workflow for the identification and delineation of relevant histological features from routinely prepared BMTs. Subsequent analysis enabled the tissue diagnosis of MPN with a high predictive accuracy (area under the curve = 0.95) and revealed clear evidence of the potential to discriminate between important MPN subtypes. Our method of visually representing abstracted megakaryocyte features in the context of analyzed patient cohorts facilitates the interpretation and monitoring of samples in a manner that is beyond conventional approaches. The automated BMT phenotyping approach described here has significant potential as an adjunct to standard genetic and molecular testing in established or suspected MPN patients, either as part of the routine diagnostic pathway or in the assessment of disease progression/response to treatment.",,doi:https://doi.org/10.1182/bloodadvances.2020002230; html:https://europepmc.org/articles/PMC7391156; pdf:https://europepmc.org/articles/PMC7391156?pdf=render; doi:https://doi.org/10.1182/bloodadvances.2020002230 @@ -1907,10 +1909,10 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 33705244,https://doi.org/10.1177/17474930211004277,Stroke risk following traumatic brain injury: Systematic review and meta-analysis.,"Turner GM, McMullan C, Aiyegbusi OL, Bem D, Marshall T, Calvert M, Mant J, Belli A.",,International journal of stroke : official journal of the International Stroke Society,2021,2021-04-04,Y,Meta-analysis; Traumatic brain injury; Stroke; Systematic review; risk,,,"

Background

Traumatic brain injury is a global health problem; worldwide, >60 million people experience a traumatic brain injury each year and incidence is rising. Traumatic brain injury has been proposed as an independent risk factor for stroke.

Aims

To investigate the association between traumatic brain injury and stroke risk.

Summary of review

We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4 December 2020. We used random-effects meta-analysis to pool hazard ratios for studies which reported stroke risk post-traumatic brain injury compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-traumatic brain injury control group, all found traumatic brain injury patients had significantly increased risk of stroke compared to controls (pooled hazard ratio 1.86; 95% confidence interval 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-traumatic brain injury, but remains significant up to five years post-traumatic brain injury. Traumatic brain injury appears to be associated with increased stroke risk regardless of severity or subtype of traumatic brain injury. There was some evidence to suggest an association between reduced stroke risk post-traumatic brain injury and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants.

Conclusion

Traumatic brain injury is an independent risk factor for stroke, regardless of traumatic brain injury severity or type. Post-traumatic brain injury review and management of risk factors for stroke may be warranted.",,doi:https://doi.org/10.1177/17474930211004277; html:https://europepmc.org/articles/PMC8193616; pdf:https://europepmc.org/articles/PMC8193616?pdf=render 33516292,https://doi.org/10.1016/s2468-2667(20)30210-3,Associations between pre-pregnancy psychosocial risk factors and infant outcomes: a population-based cohort study in England.,"Harron K, Gilbert R, Fagg J, Guttmann A, van der Meulen J.",,The Lancet. Public health,2021,2021-02-01,Y,,,,"

Background

Existing studies evaluating the association between maternal risk factors and specific infant outcomes such as birthweight, injury admissions, and mortality have mostly focused on single risk factors. We aimed to identify routinely recorded psychosocial characteristics of pregnant women most at risk of adverse infant outcomes to inform targeting of early intervention.

Methods

We created a cohort using administrative hospital data (Hospital Episode Statistics) for all births to mothers aged 15-44 years in England, UK, who gave birth on or after April 1, 2010, and who were discharged before or on March 31, 2015. We used generalised linear models to evaluate associations between psychosocial risk factors recorded in hospital records in the 2 years before the 20th week of pregnancy (ie, teenage motherhood, deprivation, pre-pregnancy hospital admissions for mental health or behavioural conditions, and pre-pregnancy hospital admissions for adversity, including drug or alcohol abuse, violence, and self-harm) and infant outcomes (ie, birthweight, unplanned admission for injury, or death from any cause, within 12 months from postnatal discharge).

Findings

Of 2 520 501 births initially assessed, 2 137 103 were eligible and were included in the birth outcome analysis. Among the eligible births, 93 279 (4·4%) were births to teenage mothers (age <20 years), 168 186 (7·9%) were births to previous teenage mothers, 51 312 (2·4%) were births to mothers who had a history of hospital admissions for mental health or behavioural conditions, 58 107 (2·7%) were births to mothers who had a history of hospital admissions for adversity, and 580 631 (27·2%) were births to mothers living in areas of high deprivation. 1 377 706 (64·5%) of births were to mothers with none of the above risk factors. Infants born to mothers with any of these risk factors had poorer outcomes than those born to mothers without these risk factors. Those born to mothers with a history of mental health or behavioural conditions were 124 g lighter (95% CI 114-134 g) than those born to mothers without these conditions. For teenage mothers compared with older mothers, 3·6% (95% CI 3·3-3·9%) more infants had an unplanned admission for injury, and there were 10·2 (95% CI 7·5-12·9) more deaths per 10 000 infants.

Interpretation

Health-care services should respond proactively to pre-pregnancy psychosocial risk factors. Our study demonstrates a need for effective interventions before, during, and after pregnancy to reduce the downstream burden on health services and prevent long-term adverse effects for children.

Funding

Wellcome Trust.",,doi:https://doi.org/10.1016/S2468-2667(20)30210-3; html:https://europepmc.org/articles/PMC7848754; pdf:https://europepmc.org/articles/PMC7848754?pdf=render 33203906,https://doi.org/10.1038/s41598-020-76518-z,Accelerated MRI-predicted brain ageing and its associations with cardiometabolic and brain disorders.,"Kolbeinsson A, Filippi S, Panagakis Y, Matthews PM, Elliott P, Dehghan A, Tzoulaki I.",,Scientific reports,2020,2020-11-17,Y,,,,"Brain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict ""healthy"" brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.",,doi:https://doi.org/10.1038/s41598-020-76518-z; html:https://europepmc.org/articles/PMC7672070; pdf:https://europepmc.org/articles/PMC7672070?pdf=render -30772400,https://doi.org/10.1016/j.neuroimage.2019.02.028,Hierarchical complexity of the adult human structural connectome.,"Smith K, Bastin ME, Cox SR, Valdés Hernández MC, Wiseman S, Escudero J, Sudlow C.",,NeuroImage,2019,2019-02-14,Y,MRI; Brain Networks; Hierarchical Complexity; Human Structural Connectome,The Human Phenome,,"The structural network of the human brain has a rich topology which many have sought to characterise using standard network science measures and concepts. However, this characterisation remains incomplete and the non-obvious features of this topology have largely confounded attempts towards comprehensive constructive modelling. This calls for new perspectives. Hierarchical complexity is an emerging paradigm of complex network topology based on the observation that complex systems are composed of hierarchies within which the roles of hierarchically equivalent nodes display highly variable connectivity patterns. Here we test the hierarchical complexity of the human structural connectomes of a group of seventy-nine healthy adults. Binary connectomes are found to be more hierarchically complex than three benchmark random network models. This provides a new key description of brain structure, revealing a rich diversity of connectivity patterns within hierarchically equivalent nodes. Dividing the connectomes into four tiers based on degree magnitudes indicates that the most complex nodes are neither those with the highest nor lowest degrees but are instead found in the middle tiers. Spatial mapping of the brain regions in each hierarchical tier reveals consistency with the current anatomical, functional and neuropsychological knowledge of the human brain. The most complex tier (Tier 3) involves regions believed to bridge high-order cognitive (Tier 1) and low-order sensorimotor processing (Tier 2). We then show that such diversity of connectivity patterns aligns with the diversity of functional roles played out across the brain, demonstrating that hierarchical complexity can characterise functional diversity strictly from the network topology.",,doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; html:https://europepmc.org/articles/PMC6503942 31794059,https://doi.org/10.1111/bjd.18778,What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.,"Blakeway H, Van-de-Velde V, Allen VB, Kravvas G, Palla L, Page MJ, Flohr C, Weller RB, Irvine AD, McPherson T, Roberts A, Williams HC, Reynolds N, Brown SJ, Paternoster L, Langan SM, (on behalf of UK TREND Eczema Network).",,The British journal of dermatology,2020,2020-02-11,Y,,,,"

Background

Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD).

Objectives

To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations.

Methods

A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis.

Results

Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions.

Conclusions

Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.",,doi:https://doi.org/10.1111/bjd.18778; html:https://europepmc.org/articles/PMC7496176; pdf:https://europepmc.org/articles/PMC7496176?pdf=render -32336304,https://doi.org/10.1192/j.eurpsy.2020.39,Prevalence and incidence of clinical outcomes in patients presenting to secondary mental health care with mood instability and sleep disturbance.,"McDonald K, Smith T, Broadbent M, Patel R, Geddes JR, Saunders KEA.",,European psychiatry : the journal of the Association of European Psychiatrists,2020,2020-04-27,Y,Sleep; Psychiatry; epidemiology; Mood; Electronic Health Records,,,"

Background

Mood instability and sleep disturbance are common symptoms in people with mental illness. Both features are clinically important and associated with poorer illness trajectories. We compared clinical outcomes in people presenting to secondary mental health care with mood instability and/or sleep disturbance with outcomes in people without either mood instability or sleep disturbance.

Methods

Data were from electronic health records of 31,391 patients ages 16-65 years presenting to secondary mental health services between 2008 and 2016. Mood instability and sleep disturbance were identified using natural language processing. Prevalence of mood instability and sleep disturbance were estimated at baseline. Incidence rate ratios were estimates for clinical outcomes including psychiatric diagnoses, prescribed medication, and hospitalization within 2-years of presentation in persons with mood instability and/or sleep disturbance compared to individuals without either symptom.

Results

Mood instability was present in 9.58%, and sleep disturbance in 26.26% of patients within 1-month of presenting to secondary mental health services. Compared with individuals without either symptom, those with mood instability and sleep disturbance showed significantly increased incidence of prescription of any psychotropic medication (incidence rate ratios [IRR] = 7.04, 95% confidence intervals [CI] 6.53-7.59), and hospitalization (IRR = 5.32, 95% CI 5.32, 4.67-6.07) within 2-years of presentation. Incidence rates of most clinical outcomes were considerably increased among persons with both mood instability and sleep disturbance, relative to persons with only one symptom.

Conclusions

Mood instability and sleep disturbance are present in a wide range of mental disorders, beyond those in which they are conventionally considered to be symptoms. They are associated with poor outcomes, particularly when they occur together. The poor prognosis associated with mood instability and sleep disorder may be, in part, because they are often treated as secondary symptoms. Mood instability and sleep disturbance need better recognition as clinical targets for treatment in their own right.",,doi:https://doi.org/10.1192/j.eurpsy.2020.39; html:https://europepmc.org/articles/PMC7355164; pdf:https://europepmc.org/articles/PMC7355164?pdf=render +30772400,https://doi.org/10.1016/j.neuroimage.2019.02.028,Hierarchical complexity of the adult human structural connectome.,"Smith K, Bastin ME, Cox SR, Valdés Hernández MC, Wiseman S, Escudero J, Sudlow C.",,NeuroImage,2019,2019-02-14,Y,MRI; Brain Networks; Hierarchical Complexity; Human Structural Connectome,The Human Phenome,,"The structural network of the human brain has a rich topology which many have sought to characterise using standard network science measures and concepts. However, this characterisation remains incomplete and the non-obvious features of this topology have largely confounded attempts towards comprehensive constructive modelling. This calls for new perspectives. Hierarchical complexity is an emerging paradigm of complex network topology based on the observation that complex systems are composed of hierarchies within which the roles of hierarchically equivalent nodes display highly variable connectivity patterns. Here we test the hierarchical complexity of the human structural connectomes of a group of seventy-nine healthy adults. Binary connectomes are found to be more hierarchically complex than three benchmark random network models. This provides a new key description of brain structure, revealing a rich diversity of connectivity patterns within hierarchically equivalent nodes. Dividing the connectomes into four tiers based on degree magnitudes indicates that the most complex nodes are neither those with the highest nor lowest degrees but are instead found in the middle tiers. Spatial mapping of the brain regions in each hierarchical tier reveals consistency with the current anatomical, functional and neuropsychological knowledge of the human brain. The most complex tier (Tier 3) involves regions believed to bridge high-order cognitive (Tier 1) and low-order sensorimotor processing (Tier 2). We then show that such diversity of connectivity patterns aligns with the diversity of functional roles played out across the brain, demonstrating that hierarchical complexity can characterise functional diversity strictly from the network topology.",,doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; html:https://europepmc.org/articles/PMC6503942 33972514,https://doi.org/10.1038/s41467-021-22338-2,Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.,"Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, Järvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.",,Nature communications,2021,2021-05-10,Y,,,,"Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.",,doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render; pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf +32336304,https://doi.org/10.1192/j.eurpsy.2020.39,Prevalence and incidence of clinical outcomes in patients presenting to secondary mental health care with mood instability and sleep disturbance.,"McDonald K, Smith T, Broadbent M, Patel R, Geddes JR, Saunders KEA.",,European psychiatry : the journal of the Association of European Psychiatrists,2020,2020-04-27,Y,Sleep; Psychiatry; epidemiology; Mood; Electronic Health Records,,,"

Background

Mood instability and sleep disturbance are common symptoms in people with mental illness. Both features are clinically important and associated with poorer illness trajectories. We compared clinical outcomes in people presenting to secondary mental health care with mood instability and/or sleep disturbance with outcomes in people without either mood instability or sleep disturbance.

Methods

Data were from electronic health records of 31,391 patients ages 16-65 years presenting to secondary mental health services between 2008 and 2016. Mood instability and sleep disturbance were identified using natural language processing. Prevalence of mood instability and sleep disturbance were estimated at baseline. Incidence rate ratios were estimates for clinical outcomes including psychiatric diagnoses, prescribed medication, and hospitalization within 2-years of presentation in persons with mood instability and/or sleep disturbance compared to individuals without either symptom.

Results

Mood instability was present in 9.58%, and sleep disturbance in 26.26% of patients within 1-month of presenting to secondary mental health services. Compared with individuals without either symptom, those with mood instability and sleep disturbance showed significantly increased incidence of prescription of any psychotropic medication (incidence rate ratios [IRR] = 7.04, 95% confidence intervals [CI] 6.53-7.59), and hospitalization (IRR = 5.32, 95% CI 5.32, 4.67-6.07) within 2-years of presentation. Incidence rates of most clinical outcomes were considerably increased among persons with both mood instability and sleep disturbance, relative to persons with only one symptom.

Conclusions

Mood instability and sleep disturbance are present in a wide range of mental disorders, beyond those in which they are conventionally considered to be symptoms. They are associated with poor outcomes, particularly when they occur together. The poor prognosis associated with mood instability and sleep disorder may be, in part, because they are often treated as secondary symptoms. Mood instability and sleep disturbance need better recognition as clinical targets for treatment in their own right.",,doi:https://doi.org/10.1192/j.eurpsy.2020.39; html:https://europepmc.org/articles/PMC7355164; pdf:https://europepmc.org/articles/PMC7355164?pdf=render 32681152,https://doi.org/10.1038/s41596-020-0343-3,Identifying unknown metabolites using NMR-based metabolic profiling techniques.,"Garcia-Perez I, Posma JM, Serrano-Contreras JI, Boulangé CL, Chan Q, Frost G, Stamler J, Elliott P, Lindon JC, Holmes E, Nicholson JK.",,Nature protocols,2020,2020-07-17,N,,,,"Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes but is hindered by a lack of automated annotation and standardized methods for structure elucidation of candidate disease biomarkers. Here we describe a system for identifying molecular species derived from nuclear magnetic resonance (NMR) spectroscopy-based metabolic phenotyping studies, with detailed information on sample preparation, data acquisition and data modeling. We provide eight different modular workflows to be followed in a recommended sequential order according to their level of difficulty. This multi-platform system involves the use of statistical spectroscopic tools such as Statistical Total Correlation Spectroscopy (STOCSY), Subset Optimization by Reference Matching (STORM) and Resolution-Enhanced (RED)-STORM to identify other signals in the NMR spectra relating to the same molecule. It also uses two-dimensional NMR spectroscopic analysis, separation and pre-concentration techniques, multiple hyphenated analytical platforms and data extraction from existing databases. The complete system, using all eight workflows, would take up to a month, as it includes multi-dimensional NMR experiments that require prolonged experiment times. However, easier identification cases using fewer steps would take 2 or 3 days. This approach to biomarker discovery is efficient and cost-effective and offers increased chemical space coverage of the metabolome, resulting in faster and more accurate assignment of NMR-generated biomarkers arising from metabolic phenotyping studies. It requires a basic understanding of MATLAB to use the statistical spectroscopic tools and analytical skills to perform solid phase extraction (SPE), liquid chromatography (LC) fraction collection, LC-NMR-mass spectroscopy and one-dimensional and two-dimensional NMR experiments.",,doi:https://doi.org/10.1038/s41596-020-0343-3 35188868,https://doi.org/10.1080/19490976.2022.2038863,The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma.,"Bosch S, Acharjee A, Quraishi MN, Rojas P, Bakkali A, Jansen EE, Brizzio Brentar M, Kuijvenhoven J, Stokkers P, Struys E, Beggs AD, Gkoutos GV, de Meij TG, de Boer NK.",,Gut microbes,2022,2022-01-01,Y,Biomarker; Surveillance; Adenoma; Colorectal Cancer; Omics,,,"The risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy (n = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities (n = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline (p = .001), ornithine (p = .02) and serine (p = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found (Bifidobacterium spp.↓, Anaerostipes spp.↓, Butyricimonas spp.↑, Faecalitalea spp.↑ and Catenibacterium spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, Faecalitalea spp. and Butyricimonas spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer.",,doi:https://doi.org/10.1080/19490976.2022.2038863; html:https://europepmc.org/articles/PMC8865277; pdf:https://europepmc.org/articles/PMC8865277?pdf=render 34240696,https://doi.org/10.2807/1560-7917.es.2021.26.27.2000004,"Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season. ","Xu Y, Lewandowski K, Downs LO, Kavanagh J, Hender T, Lumley S, Jeffery K, Foster D, Sanderson ND, Vaughan A, Morgan M, Vipond R, Carroll M, Peto T, Crook D, Walker AS, Matthews PC, Pullan ST.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-07-01,Y,,,,"BackgroundInfluenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions.AimTo evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.MethodsWe conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.ResultsCompared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.ConclusionNanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.",,doi:https://doi.org/10.2807/1560-7917.ES.2021.26.27.2000004; html:https://europepmc.org/articles/PMC8268652; pdf:https://europepmc.org/articles/PMC8268652?pdf=render @@ -1957,15 +1959,15 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 36053624,https://doi.org/10.1136/bmjpo-2022-001543,Use of parenteral nutrition in the first postnatal week in England and Wales: an observational study using real-world data.,"Webbe J, Battersby C, Longford N, Oughham K, Uthaya S, Modi N, Gale C.",,BMJ paediatrics open,2022,2022-08-01,Y,epidemiology; Neonatology,,,"

Background

Parenteral nutrition (PN) is used to provide supplemental support to neonates while enteral feeding is being established. PN is a high-cost intervention with beneficial and harmful effects. Internationally, there is substantial variation in how PN is used, and there are limited contemporary data describing use across Great Britain.

Objective

To describe PN use in the first postnatal week in infants born and admitted to neonatal care in England, Scotland and Wales.

Method

Data describing neonates admitted to National Health Service neonatal units between 1 January 2012 and 31 December 2017, extracted from routinely recorded data held the National Neonatal Research Database (NNRD); the denominator was live births, from Office for National Statistics.

Results

Over the study period 62 145 neonates were given PN in the first postnatal week (1.4% of all live births); use was higher in more preterm neonates (76% of livebirths at <28 weeks, 0.2% of term livebirths) and in neonates with lower birth weight. 15% (9181/62145) of neonates given PN in the first postnatal week were born at term. There was geographic variation in PN administration: the proportion of live births given PN within neonatal regional networks ranged from 1.0% (95% CIs 1.0 to 1.0) to 2.8% (95% CI 2.7 to 2.9).

Conclusions and relevance

Significant variation exists in neonatal PN use; it is unlikely this reflects optimal use of an expensive intervention. Research is needed to identify which babies will benefit most and which are at risk of harm from early PN.

Trial registration number

ClinicalTrials.gov: NCT03767634; registration date: 6 December 2018.",,doi:https://doi.org/10.1136/bmjpo-2022-001543; html:https://europepmc.org/articles/PMC9422803; pdf:https://europepmc.org/articles/PMC9422803?pdf=render; pdf:https://bmjpaedsopen.bmj.com/content/bmjpo/6/1/e001543.full.pdf 34480422,https://doi.org/10.1002/ehf2.13517,The genomics of heart failure: design and rationale of the HERMES consortium.,"Lumbers RT, Shah S, Lin H, Czuba T, Henry A, Swerdlow DI, Mälarstig A, Andersson C, Verweij N, Holmes MV, Ärnlöv J, Svensson P, Hemingway H, Sallah N, Almgren P, Aragam KG, Asselin G, Backman JD, Biggs ML, Bloom HL, Boersma E, Brandimarto J, Brown MR, Brunner-La Rocca HP, Carey DJ, Chaffin MD, Chasman DI, Chazara O, Chen X, Chen X, Chung JH, Chutkow W, Cleland JGF, Cook JP, de Denus S, Dehghan A, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Engström G, Esko T, Fatemifar G, Felix SB, Finan C, Ford I, Fougerousse F, Fouodjio R, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gui H, Gutmann R, Haggerty CM, van der Harst P, Hedman ÅK, Helgadottir A, Hillege H, Hyde CL, Jacob J, Jukema JW, Kamanu F, Kardys I, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Kraus B, Kuchenbaecker K, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Mann D, Margulies KB, Marston NA, März W, McMurray JJV, Melander O, Melloni G, Mordi IR, Morley MP, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Newton-Cheh C, Niessner A, Niiranen T, Nowak C, O'Donoghue ML, Owens AT, Palmer CNA, Paré G, Perola M, Perreault LL, Portilla-Fernandez E, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Roselli C, Rotter JI, Ruff CT, Sabatine MS, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stefansson K, Stender S, Stott DJ, Sveinbjörnsson G, Tammesoo ML, Tardif JC, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tuckwell D, Tyl B, Uitterlinden AG, Vaura F, Veluchamy A, Visscher PM, Völker U, Voors AA, Wang X, Wareham NJ, Weeke PE, Weiss R, White HD, Wiggins KL, Xing H, Yang J, Yang Y, Yerges-Armstrong LM, Yu B, Zannad F, Zhao F, Regeneron Genetics Center, Wilk JB, Holm H, Sattar N, Lubitz SA, Lanfear DE, Shah S, Dunn ME, Wells QS, Asselbergs FW, Hingorani AD, Dubé MP, Samani NJ, Lang CC, Cappola TP, Ellinor PT, Vasan RS, Smith JG.",,ESC heart failure,2021,2021-09-03,Y,Genetics; Biomarkers; Cardiomyopathy; Heart Failure; Association Studies,,,"

Aims

The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods and results

The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.

Conclusions

HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.",,doi:https://doi.org/10.1002/ehf2.13517; html:https://europepmc.org/articles/PMC8712846; pdf:https://europepmc.org/articles/PMC8712846?pdf=render 35876425,https://doi.org/10.1002/mds.29147,"MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia.","Reid KM, Spaull R, Salian S, Barwick K, Meyer E, Zhen J, Hirata H, Sheipouri D, Benkerroum H, Gorman KM, Papandreou A, Simpson MA, Hirano Y, Farabella I, Topf M, Grozeva D, Carss K, Smith M, Pall H, Lunt P, De Gressi S, Kamsteeg EJ, Haack TB, Carr L, Guerreiro R, Bras J, Maher ER, Scott RH, Vandenberg RJ, Raymond FL, Chong WK, Sudhakar S, Mankad K, Reith ME, Campeau PM, Harvey RJ, Kurian MA.",,Movement disorders : official journal of the Movement Disorder Society,2022,2022-07-25,Y,Dystonia; Status Dystonicus; Med27; Mppe1; Slc6a7,,,"

Background

Despite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in patients with complex neurodevelopmental disorders.

Objective

The objective of this study was to identify and characterize the underlying cause of disease in a family with two children with severe developmental delay associated with generalized dystonia and episodic status dystonicus, chorea, epilepsy, and cataracts.

Methods

Candidate genes identified by autozygosity mapping and whole-exome sequencing were characterized using cellular and vertebrate model systems.

Results

Homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1. Although the patients had features of MED27-related disorder, the SLC6A7 and MPPE1 variants were functionally investigated. SLC6A7 variant in vitro overexpression caused decreased proline transport as a result of reduced cell-surface expression, and zebrafish knockdown of slc6a7 exhibited developmental delay and fragile motor neuron morphology that could not be rescued by L-proline transporter-G396S RNA. Lastly, patient fibroblasts displayed reduced cell-surface expression of glycophosphatidylinositol-anchored proteins linked to MPPE1 dysfunction.

Conclusions

We report a family harboring a homozygous MED27 variant with additional loss-of-function SLC6A7 and MPPE1 gene variants, which potentially contribute to a blended phenotype caused by multilocus pathogenic variants. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",,doi:https://doi.org/10.1002/mds.29147; html:https://europepmc.org/articles/PMC9796674; pdf:https://europepmc.org/articles/PMC9796674?pdf=render -35143473,https://doi.org/10.1371/journal.pbio.3001531,SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.,"Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.",,PLoS biology,2022,2022-02-10,Y,,,,"Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.",,doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render 31711539,https://doi.org/10.1186/s13326-019-0211-7,Text mining brain imaging reports.,"Alex B, Grover C, Tobin R, Sudlow C, Mair G, Whiteley W.",,Journal of biomedical semantics,2019,2019-11-12,Y,Stroke Classification; Text Mining; Electronic Healthcare Records; Neuroimaging Reports,,,"

Background

With the improvements to text mining technology and the availability of large unstructured Electronic Healthcare Records (EHR) datasets, it is now possible to extract structured information from raw text contained within EHR at reasonably high accuracy. We describe a text mining system for classifying radiologists' reports of CT and MRI brain scans, assigning labels indicating occurrence and type of stroke, as well as other observations. Our system, the Edinburgh Information Extraction for Radiology reports (EdIE-R) system, which we describe here, was developed and tested on a collection of radiology reports.The work reported in this paper is based on 1168 radiology reports from the Edinburgh Stroke Study (ESS), a hospital-based register of stroke and transient ischaemic attack patients. We manually created annotations for this data in parallel with developing the rule-based EdIE-R system to identify phenotype information related to stroke in radiology reports. This process was iterative and domain expert feedback was considered at each iteration to adapt and tune the EdIE-R text mining system which identifies entities, negation and relations between entities in each report and determines report-level labels (phenotypes).

Results

The inter-annotator agreement (IAA) for all types of annotations is high at 96.96 for entities, 96.46 for negation, 95.84 for relations and 94.02 for labels. The equivalent system scores on the blind test set are equally high at 95.49 for entities, 94.41 for negation, 98.27 for relations and 96.39 for labels for the first annotator and 96.86, 96.01, 96.53 and 92.61, respectively for the second annotator.

Conclusion

Automated reading of such EHR data at such high levels of accuracies opens up avenues for population health monitoring and audit, and can provide a resource for epidemiological studies. We are in the process of validating EdIE-R in separate larger cohorts in NHS England and Scotland. The manually annotated ESS corpus will be available for research purposes on application.",,doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render +35143473,https://doi.org/10.1371/journal.pbio.3001531,SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.,"Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.",,PLoS biology,2022,2022-02-10,Y,,,,"Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.",,doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render 35337642,https://doi.org/10.1016/s2589-7500(22)00018-8,"Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.","Närhi F, Moonesinghe SR, Shenkin SD, Drake TM, Mulholland RH, Donegan C, Dunning J, Fairfield CJ, Girvan M, Hardwick HE, Ho A, Leeming G, Nguyen-Van-Tam JS, Pius R, Russell CD, Shaw CA, Spencer RG, Turtle L, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, Docherty AB, ISARIC4C investigators.",,The Lancet. Digital health,2022,2022-04-01,Y,,,,"

Background

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods

We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.

Findings

Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021.

Interpretation

Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.

Funding

UK National Institute for Health Research and UK Medical Research Council.",,doi:https://doi.org/10.1016/S2589-7500(22)00018-8; html:https://europepmc.org/articles/PMC8940185; pdf:http://www.thelancet.com/article/S2589750022000188/pdf -35112706,https://doi.org/10.1242/dmm.049257,Molecular Subtyping Resource: a user-friendly tool for rapid biological discovery from transcriptional data.,"Ahmaderaghi B, Amirkhah R, Jackson J, Lannagan TRM, Gilroy K, Malla SB, Redmond KL, Quinn G, McDade SS, ACRCelerate Consortium, Maughan T, Leedham S, Campbell ASD, Sansom OJ, Lawler M, Dunne PD.",,Disease models & mechanisms,2022,2022-03-30,Y,Bioinformatics; Rna-seq; Data Analytics,,,"Generation of transcriptional data has dramatically increased in the past decade, driving the development of analytical algorithms that enable interrogation of the biology underpinning the profiled samples. However, these resources require users to have expertise in data wrangling and analytics, reducing opportunities for biological discovery by 'wet-lab' users with a limited programming skillset. Although commercial solutions exist, costs for software access can be prohibitive for academic research groups. To address these challenges, we have developed an open source and user-friendly data analysis platform for on-the-fly bioinformatic interrogation of transcriptional data derived from human or mouse tissue, called Molecular Subtyping Resource (MouSR). This internet-accessible analytical tool, https://mousr.qub.ac.uk/, enables users to easily interrogate their data using an intuitive 'point-and-click' interface, which includes a suite of molecular characterisation options including quality control, differential gene expression, gene set enrichment and microenvironmental cell population analyses from RNA sequencing. The MouSR online tool provides a unique freely available option for users to perform rapid transcriptomic analyses and comprehensive interrogation of the signalling underpinning transcriptional datasets, which alleviates a major bottleneck for biological discovery. This article has an associated First Person interview with the first author of the paper.",,doi:https://doi.org/10.1242/dmm.049257; html:https://europepmc.org/articles/PMC8990914; doi:https://doi.org/10.1242/dmm.049257 34151270,https://doi.org/10.1136/bmjno-2021-000133,"Variation in waiting times by diagnostic category: an observational study of 1,951 referrals to a neurology outpatient clinic.","Biggin F, Howcroft T, Davies Q, Knight J, Emsley HCA.",,BMJ neurology open,2021,2021-06-03,Y,Neurology; Outpatient; Observational Study; Waiting Times; Routinely Collected Data,,,"

Objective

To investigate the frequency of diagnoses seen among new referrals to neurology outpatient services; to understand how these services are used through exploratory analysis of diagnostic tests and follow-up appointments; and to examine the waiting times between referral and appointment.

Methods

Routine data from new National Health Service appointments at a single consultant-delivered clinic between September 2016 and January 2019 were collected. These clinical data were then linked to hospital administrative data. The combined data were assigned diagnostic categories based on working diagnoses to allow further analysis using descriptive statistics.

Results

Five diagnostic categories accounted for 62% of all patients seen within the study period, the most common of which was headache disorders. Following a first appointment, 50% of all patients were offered at least one diagnostic test, and 35% were offered a follow-up appointment, with variation in both measures by diagnostic category. Waiting times from referral to appointment also varied by diagnostic category. 65% of patients with a seizure/epilepsy disorder were seen within the 18-week referral to treatment target, compared with 38% of patients with a movement disorder.

Conclusions

A small number of diagnostic categories account for a large proportion of new patients. This information could be used in policy decision-making to describe a minimum subset of categories for diagnostic coding. We found significant differences in waiting times by diagnostic category, as well as tests ordered, and follow-up offered; further investigation could address causes of variation.",,doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render +35112706,https://doi.org/10.1242/dmm.049257,Molecular Subtyping Resource: a user-friendly tool for rapid biological discovery from transcriptional data.,"Ahmaderaghi B, Amirkhah R, Jackson J, Lannagan TRM, Gilroy K, Malla SB, Redmond KL, Quinn G, McDade SS, ACRCelerate Consortium, Maughan T, Leedham S, Campbell ASD, Sansom OJ, Lawler M, Dunne PD.",,Disease models & mechanisms,2022,2022-03-30,Y,Bioinformatics; Rna-seq; Data Analytics,,,"Generation of transcriptional data has dramatically increased in the past decade, driving the development of analytical algorithms that enable interrogation of the biology underpinning the profiled samples. However, these resources require users to have expertise in data wrangling and analytics, reducing opportunities for biological discovery by 'wet-lab' users with a limited programming skillset. Although commercial solutions exist, costs for software access can be prohibitive for academic research groups. To address these challenges, we have developed an open source and user-friendly data analysis platform for on-the-fly bioinformatic interrogation of transcriptional data derived from human or mouse tissue, called Molecular Subtyping Resource (MouSR). This internet-accessible analytical tool, https://mousr.qub.ac.uk/, enables users to easily interrogate their data using an intuitive 'point-and-click' interface, which includes a suite of molecular characterisation options including quality control, differential gene expression, gene set enrichment and microenvironmental cell population analyses from RNA sequencing. The MouSR online tool provides a unique freely available option for users to perform rapid transcriptomic analyses and comprehensive interrogation of the signalling underpinning transcriptional datasets, which alleviates a major bottleneck for biological discovery. This article has an associated First Person interview with the first author of the paper.",,doi:https://doi.org/10.1242/dmm.049257; html:https://europepmc.org/articles/PMC8990914; doi:https://doi.org/10.1242/dmm.049257 33174830,https://doi.org/10.1099/mgen.0.000453,Optimized use of Oxford Nanopore flowcells for hybrid assemblies.,"Lipworth S, Pickford H, Sanderson N, Chau KK, Kavanagh J, Barker L, Vaughan A, Swann J, Andersson M, Jeffery K, Morgan M, Peto TEA, Crook DW, Stoesser N, Walker AS.",,Microbial genomics,2020,2020-11-01,Y,Enterobacteriaceae; Hybrid Assembly; Nanopore Sequencing; Bacterial Genomics; Long-read Assembly,,,"Hybrid assemblies are highly valuable for studies of Enterobacteriaceae due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in antimicrobial resistance/virulence). The widespread application of this technique is currently primarily limited by cost. Recent data have suggested that non-inferior, and even superior, hybrid assemblies can be produced using a fraction of the total output from a multiplexed nanopore [Oxford Nanopore Technologies (ONT)] flowcell run. In this study we sought to determine the optimal minimal running time for flowcells when acquiring reads for hybrid assembly. We then evaluated whether the ONT wash kit might allow users to exploit shorter running times by sequencing multiple libraries per flowcell. After 24 h of sequencing, most chromosomes and plasmids had circularized and there was no benefit associated with longer running times. Quality was similar at 12 h, suggesting that shorter running times are likely to be acceptable for certain applications (e.g. plasmid genomics). The ONT wash kit was highly effective in removing DNA between libraries. Contamination between libraries did not appear to affect subsequent hybrid assemblies, even when the same barcodes were used successively on a single flowcell. Utilizing shorter run times in combination with between-library nuclease washes allows at least 36 Enterobacteriaceae isolates to be sequenced per flowcell, significantly reducing the per-isolate sequencing cost. Ultimately this will facilitate large-scale studies utilizing hybrid assembly, advancing our understanding of the genomics of key human pathogens.",,doi:https://doi.org/10.1099/mgen.0.000453; html:https://europepmc.org/articles/PMC7725331; pdf:https://europepmc.org/articles/PMC7725331?pdf=render 34446501,https://doi.org/10.1136/bmjopen-2021-052629,Using patient-reported outcome measures during the management of patients with end-stage kidney disease requiring treatment with haemodialysis (PROM-HD): a qualitative study.,"Anderson NE, McMullan C, Calvert M, Dutton M, Cockwell P, Aiyegbusi OL, Kyte D.",,BMJ open,2021,2021-08-26,Y,Dialysis; Nephrology; Telemedicine; Qualitative Research; End Stage Renal Failure,,,"

Objectives

Patients undergoing haemodialysis report elevated symptoms and reduced health-related quality of life, and often prioritise improvements in psychosocial well-being over long-term survival. Systematic collection and use of patient-reported outcomes (PROs) may help support tailored healthcare and improve outcomes. This study investigates the methodological basis for routine PRO assessment, particularly using electronic formats (ePROs), to maximise the potential of PRO use, through exploration of the experiences, views and perceptions of patients and healthcare professionals (HCPs) on implementation and use of PROs in haemodialysis settings.

Study design

Qualitative study.

Setting and participants

Semistructured interviews with 22 patients undergoing haemodialysis, and 17 HCPs in the UK.

Analytical approach

Transcripts were analysed deductively using the Consolidated Framework for Implementation Research (CFIR) and inductively using thematic analysis.

Results

For effective implementation, the potential value of PROs needs to be demonstrated empirically to stakeholders. Any intervention must remain flexible enough for individual and aggregate use, measuring outcomes that matter to patients and clinicians, while maintaining operational simplicity. Any implementation must sit within a wider framework of education and support for both patients and clinicians who demonstrate varying previous experience of using PROs and often confuse related concepts. Implementation plans must recognise the multidimensionality of end-stage kidney disease and treatment by haemodialysis, while acknowledging the associated challenges of delivering care in a highly specialised environment. To support implementation, careful consideration needs to be given to barriers and facilitators including effective leadership, the role of champions, effective launch and ongoing evaluation.

Conclusions

Using the CFIR to explore the experiences, views and perceptions of key stakeholders, this study identified key factors at organisational and individual levels which could assist effective implementation of ePROs in haemodialysis settings. Further research will be required to evaluate subsequent ePRO interventions to demonstrate the impact and benefit to the dialysis community.",,doi:https://doi.org/10.1136/bmjopen-2021-052629; html:https://europepmc.org/articles/PMC8395280; pdf:https://europepmc.org/articles/PMC8395280?pdf=render -36845321,https://doi.org/10.12688/wellcomeopenres.17403.2,"Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.","Moreno-Martos D, Verhamme K, Ostropolets A, Kostka K, Duarte-Sales T, Prieto-Alhambra D, Alshammari TM, Alghoul H, Ahmed WU, Blacketer C, DuVall S, Lai L, Matheny M, Nyberg F, Posada J, Rijnbeek P, Spotnitz M, Sena A, Shah N, Suchard M, Chan You S, Hripcsak G, Ryan P, Morales D.",,Wellcome open research,2022,2022-03-24,Y,COPD; Coronavirus; Epidemiology.; Sars-cov-2; Covid,,,"Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.",,doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render 32423943,https://doi.org/10.1136/bmjopen-2020-038974,Study protocol for a multicentre longitudinal mixed methods study to explore the Outcomes of ChildrEn and fAmilies in the first year after paediatric Intensive Care: the OCEANIC study.,"Manning JC, Latour JM, Curley MAQ, Draper ES, Jilani T, Quinlan PR, Watson RS, Rennick JE, Colville G, Pinto N, Latif A, Popejoy E, Coad J, OCEANIC Study Investigators.",,BMJ open,2020,2020-05-17,Y,Qualitative Research; Statistics & Research Methods; Paediatric Intensive & Critical Care,,,"

Introduction

Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission.

Methods and analysis

A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data.

Ethics and dissemination

The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results].",,doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render +36845321,https://doi.org/10.12688/wellcomeopenres.17403.2,"Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.","Moreno-Martos D, Verhamme K, Ostropolets A, Kostka K, Duarte-Sales T, Prieto-Alhambra D, Alshammari TM, Alghoul H, Ahmed WU, Blacketer C, DuVall S, Lai L, Matheny M, Nyberg F, Posada J, Rijnbeek P, Spotnitz M, Sena A, Shah N, Suchard M, Chan You S, Hripcsak G, Ryan P, Morales D.",,Wellcome open research,2022,2022-03-24,Y,COPD; Coronavirus; Epidemiology.; Sars-cov-2; Covid,,,"Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.",,doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render 31331193,https://doi.org/10.1161/circulationaha.119.041546,Impact of ADCY9 Genotype on Response to Anacetrapib.,"Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R, HPS3/TIMI55–REVEAL Collaborative Group.",,Circulation,2019,2019-07-23,Y,Randomized controlled trial; Pharmacogenetics; Anacetrapib; Cholesterol Ester Transfer Protein; Adenylate Cyclase 9,"Better, Faster and More Efficient Clinical Trials",,"

Background

Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by ADCY9 genotype, prompting the ongoing dal-GenE trial in individuals with a particular genetic profile. The randomized placebo-controlled REVEAL trial (Randomized Evaluation of the Effects of Anacetrapib through Lipid-Modification) demonstrated the clinical efficacy of the CETP inhibitor anacetrapib among patients with preexisting atherosclerotic vascular disease. In the present study, we examined the impact of ADCY9 genotype on response to anacetrapib in the REVEAL trial.

Methods

Individuals with stable atherosclerotic vascular disease who were treated with intensive atorvastatin therapy received either anacetrapib 100 mg daily or matching placebo. Cox proportional hazards models, adjusted for the first 5 principal components of ancestry, were used to estimate the effects of allocation to anacetrapib on major vascular events (a composite of coronary death, myocardial infarction, coronary revascularization, or presumed ischemic stroke) and the interaction with ADCY9 rs1967309 genotype.

Results

Among 19 210 genotyped individuals of European ancestry, 2504 (13.0%) had a first major vascular event during 4 years median follow-up: 1216 (12.6%) among anacetrapib-allocated participants and 1288 (13.4%) among placebo-allocated participants. Proportional reductions in the risk of major vascular events with anacetrapib did not differ significantly by ADCY9 genotype: hazard ratio (HR) = 0.92 (95% CI, 0.81-1.05) for GG; HR = 0.94 (95% CI, 0.84-1.06) for AG; and HR = 0.93 (95% CI, 0.76-1.13) for AA genotype carriers, respectively; genotypic P for interaction = 0.96. Furthermore, there were no associations between ADCY9 genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib.

Conclusions

The REVEAL trial is the single largest study to date evaluating the ADCY9 pharmacogenetic interaction. It provides no support for the hypothesis that ADCY9 genotype is materially relevant to the clinical effects of the CETP inhibitor anacetrapib. The ongoing dal-GenE study will provide direct evidence as to whether there is any specific pharmacogenetic interaction with dalcetrapib.

Clinical trial registration

URL: https://www.

Clinicaltrials

gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041546; html:https://europepmc.org/articles/PMC6749971; pdf:https://europepmc.org/articles/PMC6749971?pdf=render; doi:https://doi.org/10.1161/circulationaha.119.041546 30819382,https://doi.org/10.1016/j.jchf.2019.01.009,Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.,"Bots SH, Groepenhoff F, Eikendal ALM, Tannenbaum C, Rochon PA, Regitz-Zagrosek V, Miller VM, Day D, Asselbergs FW, den Ruijter HM.",,JACC. Heart failure,2019,2019-03-01,N,Women; Sex differences; Heart Failure; Adverse drug reactions; Sex-specific Reporting,The Human Phenome,,"OBJECTIVES:This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication. BACKGROUND:Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs. METHODS:A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF. RESULTS:The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine. CONCLUSIONS:These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.",,doi:https://doi.org/10.1016/j.jchf.2019.01.009 36812516,https://doi.org/10.1371/journal.pdig.0000007,A proteomic survival predictor for COVID-19 patients in intensive care.,"Demichev V, Tober-Lau P, Nazarenko T, Lemke O, Kaur Aulakh S, Whitwell HJ, Röhl A, Freiwald A, Mittermaier M, Szyrwiel L, Ludwig D, Correia-Melo C, Lippert LJ, Helbig ET, Stubbemann P, Olk N, Thibeault C, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Spies C, Edel A, Müller NB, Enghard P, Zelezniak A, Bellmann-Weiler R, Weiss G, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Müller-Redetzky H, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Kurth F, Ralser M.",,PLOS digital health,2022,2022-01-18,Y,,,,"Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.",,doi:https://doi.org/10.1371/journal.pdig.0000007; html:https://europepmc.org/articles/PMC9931303; pdf:https://europepmc.org/articles/PMC9931303?pdf=render @@ -1977,7 +1979,7 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 32880390,https://doi.org/10.1210/clinem/dgaa627,"Systemic Corticosteroids and Mortality in Severe and Critical COVID-19 Patients in Wuhan, China. ","Wu J, Huang J, Zhu G, Liu Y, Xiao H, Zhou Q, Si X, Yi H, Wang C, Yang D, Chen S, Liu X, Liu Z, Wang Q, Lv Q, Huang Y, Yu Y, Guan X, Li Y, Nirantharakumar K, Cheng K, Peng S, Xiao H.",,The Journal of clinical endocrinology and metabolism,2020,2020-12-01,Y,,,,"Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY). To identify whether corticosteroids were beneficial to COVID-19 patients. A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.",,doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render 32156302,https://doi.org/10.1186/s13326-020-00220-2,Temporal information extraction from mental health records to identify duration of untreated psychosis.,"Viani N, Kam J, Yin L, Bittar A, Dutta R, Patel R, Stewart R, Velupillai S.",,Journal of biomedical semantics,2020,2020-03-10,Y,Schizophrenia; Mental health; Electronic Health Records; Natural Language Processing; Temporal Information Extraction,,,"

Background

Duration of untreated psychosis (DUP) is an important clinical construct in the field of mental health, as longer DUP can be associated with worse intervention outcomes. DUP estimation requires knowledge about when psychosis symptoms first started (symptom onset), and when psychosis treatment was initiated. Electronic health records (EHRs) represent a useful resource for retrospective clinical studies on DUP, but the core information underlying this construct is most likely to lie in free text, meaning it is not readily available for clinical research. Natural Language Processing (NLP) is a means to addressing this problem by automatically extracting relevant information in a structured form. As a first step, it is important to identify appropriate documents, i.e., those that are likely to include the information of interest. Next, temporal information extraction methods are needed to identify time references for early psychosis symptoms. This NLP challenge requires solving three different tasks: time expression extraction, symptom extraction, and temporal ""linking"". In this study, we focus on the first step, using two relevant EHR datasets.

Results

We applied a rule-based NLP system for time expression extraction that we had previously adapted to a corpus of mental health EHRs from patients with a diagnosis of schizophrenia (first referrals). We extended this work by applying this NLP system to a larger set of documents and patients, to identify additional texts that would be relevant for our long-term goal, and developed a new corpus from a subset of these new texts (early intervention services). Furthermore, we added normalized value annotations (""2011-05"") to the annotated time expressions (""May 2011"") in both corpora. The finalized corpora were used for further NLP development and evaluation, with promising results (normalization accuracy 71-86%). To highlight the specificities of our annotation task, we also applied the final adapted NLP system to a different temporally annotated clinical corpus.

Conclusions

Developing domain-specific methods is crucial to address complex NLP tasks such as symptom onset extraction and retrospective calculation of duration of a preclinical syndrome. To the best of our knowledge, this is the first clinical text resource annotated for temporal entities in the mental health domain.",,doi:https://doi.org/10.1186/s13326-020-00220-2; html:https://europepmc.org/articles/PMC7063705; pdf:https://europepmc.org/articles/PMC7063705?pdf=render 33933206,https://doi.org/10.1016/s0140-6736(21)00676-0,"Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-05-01,Y,,,,"

Background

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001).

Interpretation

In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,doi:https://doi.org/10.1016/S0140-6736(21)00676-0; html:https://europepmc.org/articles/PMC8084355; doi:https://doi.org/10.1016/s0140-6736(21)00676-0 -32435697,https://doi.org/10.1038/s41746-020-0267-x,Generation and evaluation of artificial mental health records for Natural Language Processing.,"Ive J, Viani N, Kam J, Yin L, Verma S, Puntis S, Cardinal RN, Roberts A, Stewart R, Velupillai S.",,NPJ digital medicine,2020,2020-05-14,Y,Medical research; Scientific Community,,,"A serious obstacle to the development of Natural Language Processing (NLP) methods in the clinical domain is the accessibility of textual data. The mental health domain is particularly challenging, partly because clinical documentation relies heavily on free text that is difficult to de-identify completely. This problem could be tackled by using artificial medical data. In this work, we present an approach to generate artificial clinical documents. We apply this approach to discharge summaries from a large mental healthcare provider and discharge summaries from an intensive care unit. We perform an extensive intrinsic evaluation where we (1) apply several measures of text preservation; (2) measure how much the model memorises training data; and (3) estimate clinical validity of the generated text based on a human evaluation task. Furthermore, we perform an extrinsic evaluation by studying the impact of using artificial text in a downstream NLP text classification task. We found that using this artificial data as training data can lead to classification results that are comparable to the original results. Additionally, using only a small amount of information from the original data to condition the generation of the artificial data is successful, which holds promise for reducing the risk of these artificial data retaining rare information from the original data. This is an important finding for our long-term goal of being able to generate artificial clinical data that can be released to the wider research community and accelerate advances in developing computational methods that use healthcare data.",,doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render +32435697,https://doi.org/10.1038/s41746-020-0267-x,Generation and evaluation of artificial mental health records for Natural Language Processing.,"Ive J, Viani N, Kam J, Yin L, Verma S, Puntis S, Cardinal RN, Roberts A, Stewart R, Velupillai S.",,NPJ digital medicine,2020,2020-05-14,Y,Medical research; Scientific Community,,,"A serious obstacle to the development of Natural Language Processing (NLP) methods in the clinical domain is the accessibility of textual data. The mental health domain is particularly challenging, partly because clinical documentation relies heavily on free text that is difficult to de-identify completely. This problem could be tackled by using artificial medical data. In this work, we present an approach to generate artificial clinical documents. We apply this approach to discharge summaries from a large mental healthcare provider and discharge summaries from an intensive care unit. We perform an extensive intrinsic evaluation where we (1) apply several measures of text preservation; (2) measure how much the model memorises training data; and (3) estimate clinical validity of the generated text based on a human evaluation task. Furthermore, we perform an extrinsic evaluation by studying the impact of using artificial text in a downstream NLP text classification task. We found that using this artificial data as training data can lead to classification results that are comparable to the original results. Additionally, using only a small amount of information from the original data to condition the generation of the artificial data is successful, which holds promise for reducing the risk of these artificial data retaining rare information from the original data. This is an important finding for our long-term goal of being able to generate artificial clinical data that can be released to the wider research community and accelerate advances in developing computational methods that use healthcare data.",,doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render; pdf:https://www.nature.com/articles/s41746-020-0267-x.pdf 31197928,https://doi.org/10.1002/pds.4811,Methods to generate and validate a Pregnancy Register in the UK Clinical Practice Research Datalink primary care database.,"Minassian C, Williams R, Meeraus WH, Smeeth L, Campbell OMR, Thomas SL.",,Pharmacoepidemiology and drug safety,2019,2019-06-13,Y,Pregnancy; United Kingdom; Pregnancy Outcome; Pharmacoepidemiology; Electronic Health Records; Pregnancy Trimesters,"Applied Analytics, The Human Phenome",,"

Purpose

Primary care databases are increasingly used for researching pregnancy, eg, the effects of maternal drug exposures. However, ascertaining pregnancies, their timing, and outcomes in these data is challenging. While individual studies have adopted different methods, no systematic approach to characterise all pregnancies in a primary care database has yet been published. Therefore, we developed a new algorithm to establish a Pregnancy Register in the UK Clinical Practice Research Datalink (CPRD) GOLD primary care database.

Methods

We compiled over 4000 read and entity codes to identify pregnancy-related records among women aged 11 to 49 years in CPRD GOLD. Codes were categorised by the stage or outcome of pregnancy to facilitate delineation of pregnancy episodes. We constructed hierarchical rule systems to handle information from multiple sources. We assessed the validity of the Register to identify pregnancy outcomes by comparing our results to linked hospitalisation records and Office for National Statistics population rates.

Results

Our algorithm identified 5.8 million pregnancies among 2.4 million women (January 1987-February 2018). We observed close agreement with hospitalisation data regarding completeness of pregnancy outcomes (91% sensitivity for deliveries and 77% for pregnancy losses) and their timing (median 0 days difference, interquartile range 0-2 days). Miscarriage and prematurity rates were consistent with population figures, although termination and, to a lesser extent, live birth rates were underestimated in the Register.

Conclusions

The Pregnancy Register offers huge research potential because of its large size, high completeness, and availability. Further validation work is underway to enhance this data resource and identify optimal approaches for its use.",,doi:https://doi.org/10.1002/pds.4811; html:https://europepmc.org/articles/PMC6618019; pdf:https://europepmc.org/articles/PMC6618019?pdf=render 33248277,https://doi.org/10.1016/j.jclinepi.2020.11.014,Text-mining in electronic healthcare records can be used as efficient tool for screening and data collection in cardiovascular trials: a multicenter validation study.,"van Dijk WB, Fiolet ATL, Schuit E, Sammani A, Groenhof TKJ, van der Graaf R, de Vries MC, Alings M, Schaap J, Asselbergs FW, Grobbee DE, Groenwold RHH, Mosterd A.",,Journal of clinical epidemiology,2021,2020-11-25,N,Screening; Recruitment; trials; Multicenter; cardiovascular; Text-mining; Data-mining; Electronic Medical Records (Emrs); Data-collections; Electronic Healthcare Records (Ehrs); Lodoco2,,,"

Objective

This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial.

Study design and setting

In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel.

Results

Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%).

Conclusion

Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information.",,doi:https://doi.org/10.1016/j.jclinepi.2020.11.014 34319235,https://doi.org/10.2196/28873,Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH): Protocol for a Prospective Observational Study.,"Ranjan Y, Althobiani M, Jacob J, Orini M, Dobson RJ, Porter J, Hurst J, Folarin AA.",,JMIR research protocols,2021,2021-10-07,Y,Lung diseases; Mental health; Remote Monitoring; Respiratory Health; Internet Of Things; Mhealth; Mobile Health; Wearables; Covid-19; Cardiopulmonary Diseases,,,"

Background

Chronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.

Objective

The primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.

Methods

Twenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.

Results

The Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.

Conclusions

The RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.

Trial registration

ISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601.

International registered report identifier (irrid)

PRR1-10.2196/28873.",,doi:https://doi.org/10.2196/28873; html:https://europepmc.org/articles/PMC8500349 @@ -2000,13 +2002,13 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 34812717,https://doi.org/10.1099/mgen.0.000700,Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study. ,"Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.",,Microbial genomics,2021,2021-11-01,Y,,,,"Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.",,doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render 34022072,https://doi.org/10.1002/14651858.cd012721.pub3,Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction.,"Martin N, Manoharan K, Davies C, Lumbers RT.",,The Cochrane database of systematic reviews,2021,2021-05-22,N,,,,"

Background

Beta-blockers and inhibitors of the renin-angiotensin-aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction (LVEF); a review of the evidence is required to determine whether these treatments are beneficial for people with heart failure with preserved ejection fraction (HFpEF).

Objectives

To assess the effects of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with HFpEF.

Search methods

We updated searches of CENTRAL, MEDLINE, Embase, and one clinical trial register on 14 May 2020 to identify eligible studies, with no language or date restrictions. We checked references from trial reports and review articles for additional studies.  SELECTION CRITERIA: We included randomised controlled trials with a parallel group design, enrolling adults with HFpEF, defined by LVEF greater than 40%.

Data collection and analysis

We used standard methodological procedures expected by Cochrane.

Main results

We included 41 randomised controlled trials (231 reports), totalling 23,492 participants across all comparisons. The risk of bias was frequently unclear and only five studies had a low risk of bias in all domains. Beta-blockers (BBs) We included 10 studies (3087 participants) investigating BBs. Five studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 30 years to 81 years. A possible reduction in cardiovascular mortality was observed (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.99; number needed to treat for an additional benefit (NNTB) 25; 1046 participants; three studies), however, the certainty of evidence was low. There may be little to no effect on all-cause mortality (RR 0.82, 95% CI 0.67 to 1.00; 1105 participants; four studies; low-certainty evidence). The effects on heart failure hospitalisation, hyperkalaemia, and quality of life remain uncertain. Mineralocorticoid receptor antagonists (MRAs) We included 13 studies (4459 participants) investigating MRA. Eight studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 54.5 to 80 years. Pooled analysis indicated that MRA treatment probably reduces heart failure hospitalisation (RR 0.82, 95% CI 0.69 to 0.98; NNTB = 41; 3714 participants; three studies; moderate-certainty evidence). However, MRA treatment probably has little or no effect on all-cause mortality (RR 0.91, 95% CI 0.78 to 1.06; 4207 participants; five studies; moderate-certainty evidence) and cardiovascular mortality (RR 0.90, 95% CI 0.74 to 1.11; 4070 participants; three studies; moderate-certainty evidence). MRA treatment may have little or no effect on quality of life measures (mean difference (MD) 0.84, 95% CI -2.30 to 3.98; 511 participants; three studies; low-certainty evidence). MRA treatment was associated with a higher risk of hyperkalaemia (RR 2.11, 95% CI 1.77 to 2.51; number needed to treat for an additional harmful outcome (NNTH) = 11; 4291 participants; six studies; high-certainty evidence). Angiotensin-converting enzyme inhibitors (ACEIs) We included eight studies (2061 participants) investigating ACEIs. Three studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 70 to 82 years. Pooled analyses with moderate-certainty evidence suggest that ACEI treatment likely has little or no effect on cardiovascular mortality (RR 0.93, 95% CI 0.61 to 1.42; 945 participants; two studies), all-cause mortality (RR 1.04, 95% CI 0.75 to 1.45; 1187 participants; five studies) and heart failure hospitalisation (RR 0.86, 95% CI 0.64 to 1.15; 1019 participants; three studies), and may result in little or no effect on the quality of life (MD -0.09, 95% CI -3.66 to 3.48; 154 participants; two studies; low-certainty evidence). The effects on hyperkalaemia remain uncertain. Angiotensin receptor blockers (ARBs) Eight studies (8755 participants) investigating ARBs were included. Five studies used a placebo comparator and in three the comparator was usual care. The mean age of participants ranged from 61 to 75 years. Pooled analyses with high certainty of evidence suggest that ARB treatment has little or no effect on cardiovascular mortality (RR 1.02, 95% 0.90 to 1.14; 7254 participants; three studies), all-cause mortality (RR 1.01, 95% CI 0.92 to 1.11; 7964 participants; four studies), heart failure hospitalisation (RR 0.92, 95% CI 0.83 to 1.02; 7254 participants; three studies), and quality of life (MD 0.41, 95% CI -0.86 to 1.67; 3117 participants; three studies). ARB was associated with a higher risk of hyperkalaemia (RR 1.88, 95% CI 1.07 to 3.33; 7148 participants; two studies; high-certainty evidence). Angiotensin receptor neprilysin inhibitors (ARNIs) Three studies (7702 participants) investigating ARNIs were included. Two studies used ARBs as the comparator and one used standardised medical therapy, based on participants' established treatments at enrolment. The mean age of participants ranged from 71 to 73 years. Results suggest that ARNIs may have little or no effect on cardiovascular mortality (RR 0.96, 95% CI 0.79 to 1.15; 4796 participants; one study; moderate-certainty evidence), all-cause mortality (RR 0.97, 95% CI 0.84 to 1.11; 7663 participants; three studies; high-certainty evidence), or quality of life (high-certainty evidence). However, ARNI treatment may result in a slight reduction in heart failure hospitalisation, compared to usual care (RR 0.89, 95% CI 0.80 to 1.00; 7362 participants; two studies; moderate-certainty evidence). ARNI treatment was associated with a reduced risk of hyperkalaemia compared with valsartan (RR 0.88, 95% CI 0.77 to 1.01; 5054 participants; two studies; moderate-certainty evidence).

Authors' conclusions

There is evidence that MRA and ARNI treatment in HFpEF probably reduces heart failure hospitalisation but probably has little or no effect on cardiovascular mortality and quality of life. BB treatment may reduce the risk of cardiovascular mortality, however, further trials are needed. The current evidence for BBs, ACEIs, and ARBs is limited and does not support their use in HFpEF in the absence of an alternative indication. Although MRAs and ARNIs are probably effective at reducing the risk of heart failure hospitalisation, the treatment effect sizes are modest. There is a need for improved approaches to patient stratification to identify the subgroup of patients who are most likely to benefit from MRAs and ARNIs, as well as for an improved understanding of disease biology, and for new therapeutic approaches.",,doi:https://doi.org/10.1002/14651858.CD012721.pub3; html:https://europepmc.org/articles/PMC8140651; pdf:https://europepmc.org/articles/PMC8140651?pdf=render; doi:https://doi.org/10.1002/14651858.cd012721.pub3 36315390,https://doi.org/10.1002/eat.23834,"Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.","Davies HL, Hübel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",,The International journal of eating disorders,2023,2022-10-31,Y,Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation,,,"

Objective

The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.

Method

Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.

Results

Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.

Discussion

Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.

Public significance

In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",,doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render -35484151,https://doi.org/10.1038/s41467-022-29932-y,Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.,"Richardson TG, Crouch DJM, Power GM, Morales-Berstein F, Hazelwood E, Fang S, Cho Y, Inshaw JRJ, Robertson CC, Sidore C, Cucca F, Rich SS, Todd JA, Davey Smith G.",,Nature communications,2022,2022-04-28,Y,,,,"The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.20 to 3.50, P = 0.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR = 2.32, 95% CI = 1.21 to 4.42, P = 0.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n = 15,573 cases and n = 158,408 controls (OR = 1.94, 95% CI = 1.21 to 3.12, P = 0.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse.",,doi:https://doi.org/10.1038/s41467-022-29932-y; html:https://europepmc.org/articles/PMC9051135; pdf:https://europepmc.org/articles/PMC9051135?pdf=render 33323250,https://doi.org/10.1016/s2589-7500(19)30121-9,"Development and validation of multivariable prediction models of remission, recovery, and quality of life outcomes in people with first episode psychosis: a machine learning approach.","Leighton SP, Upthegrove R, Krishnadas R, Benros ME, Broome MR, Gkoutos GV, Liddle PF, Singh SP, Everard L, Jones PB, Fowler D, Sharma V, Freemantle N, Christensen RHB, Albert N, Nordentoft M, Schwannauer M, Cavanagh J, Gumley AI, Birchwood M, Mallikarjun PK.",,The Lancet. Digital health,2019,2019-09-12,N,,,,"

Background

Outcomes for people with first-episode psychosis are highly heterogeneous. Few reliable validated methods are available to predict the outcome for individual patients in the first clinical contact. In this study, we aimed to build multivariable prediction models of 1-year remission and recovery outcomes using baseline clinical variables in people with first-episode psychosis.

Methods

In this machine learning approach, we applied supervised machine learning, using regularised regression and nested leave-one-site-out cross-validation, to baseline clinical data from the English Evaluating the Development and Impact of Early Intervention Services (EDEN) study (n=1027), to develop and internally validate prediction models at 1-year follow-up. We assessed four binary outcomes that were recorded at 1 year: symptom remission, social recovery, vocational recovery, and quality of life (QoL). We externally validated the prediction models by selecting from the top predictor variables identified in the internal validation models the variables shared with the external validation datasets comprised of two Scottish longitudinal cohort studies (n=162) and the OPUS trial, a randomised controlled trial of specialised assertive intervention versus standard treatment (n=578).

Findings

The performance of prediction models was robust for the four 1-year outcomes of symptom remission (area under the receiver operating characteristic curve [AUC] 0·703, 95% CI 0·664-0·742), social recovery (0·731, 0·697-0·765), vocational recovery (0·736, 0·702-0·771), and QoL (0·704, 0·667-0·742; p<0·0001 for all outcomes), on internal validation. We externally validated the outcomes of symptom remission (AUC 0·680, 95% CI 0·587-0·773), vocational recovery (0·867, 0·805-0·930), and QoL (0·679, 0·522-0·836) in the Scottish datasets, and symptom remission (0·616, 0·553-0·679), social recovery (0·573, 0·504-0·643), vocational recovery (0·660, 0·610-0·710), and QoL (0·556, 0·481-0·631) in the OPUS dataset.

Interpretation

In our machine learning analysis, we showed that prediction models can reliably and prospectively identify poor remission and recovery outcomes at 1 year for patients with first-episode psychosis using baseline clinical variables at first clinical contact.

Funding

Lundbeck Foundation.",,doi:https://doi.org/10.1016/S2589-7500(19)30121-9 +35484151,https://doi.org/10.1038/s41467-022-29932-y,Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.,"Richardson TG, Crouch DJM, Power GM, Morales-Berstein F, Hazelwood E, Fang S, Cho Y, Inshaw JRJ, Robertson CC, Sidore C, Cucca F, Rich SS, Todd JA, Davey Smith G.",,Nature communications,2022,2022-04-28,Y,,,,"The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.20 to 3.50, P = 0.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR = 2.32, 95% CI = 1.21 to 4.42, P = 0.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n = 15,573 cases and n = 158,408 controls (OR = 1.94, 95% CI = 1.21 to 3.12, P = 0.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse.",,doi:https://doi.org/10.1038/s41467-022-29932-y; html:https://europepmc.org/articles/PMC9051135; pdf:https://europepmc.org/articles/PMC9051135?pdf=render 32597303,https://doi.org/10.1080/15476286.2020.1777768,Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples.,"Curion F, Handel AE, Attar M, Gallone G, Bowden R, Cader MZ, Clark MB.",,RNA biology,2020,2020-06-28,Y,Method; Gene Expression; Rna-seq; Targeted Rna Sequencing; Low-input Sequencing; Stem-cell-derived Neurons; Captureseq,,,"RNA-seq is the standard method for profiling gene expression in many biological systems. Due to the wide dynamic range and complex nature of the transcriptome, RNA-seq provides an incomplete characterization, especially of lowly expressed genes and transcripts. Targeted RNA sequencing (RNA CaptureSeq) focuses sequencing on genes of interest, providing exquisite sensitivity for transcript detection and quantification. However, uses of CaptureSeq have focused on bulk samples and its performance on very small populations of cells is unknown. Here we show CaptureSeq greatly enhances transcriptomic profiling of target genes in ultra-low-input samples and provides equivalent performance to that on bulk samples. We validate the performance of CaptureSeq using multiple probe sets on samples of iPSC-derived cortical neurons. We demonstrate up to 275-fold enrichment for target genes, the detection of 10% additional genes and a greater than 5-fold increase in identified gene isoforms. Analysis of spike-in controls demonstrated CaptureSeq improved both detection sensitivity and expression quantification. Comparison to the CORTECON database of cerebral cortex development revealed CaptureSeq enhanced the identification of sample differentiation stage. CaptureSeq provides sensitive, reliable and quantitative expression measurements on hundreds-to-thousands of target genes from ultra-low-input samples and has the potential to greatly enhance transcriptomic profiling when samples are limiting.",,doi:https://doi.org/10.1080/15476286.2020.1777768; html:https://europepmc.org/articles/PMC7746246; pdf:https://europepmc.org/articles/PMC7746246?pdf=render 32095773,https://doi.org/10.1159/000503957,Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative.,"Coran P, Goldsack JC, Grandinetti CA, Bakker JP, Bolognese M, Dorsey ER, Vasisht K, Amdur A, Dell C, Helfgott J, Kirchoff M, Miller CJ, Narayan A, Patel D, Peterson B, Ramirez E, Schiller D, Switzer T, Wing L, Forrest A, Doherty A.",,Digital biomarkers,2019,2019-09-01,N,Clinical Trials; Regulatory Approval; Wearable Sensors; Mobile Technologies,"Better, Faster and More Efficient Clinical Trials",,"Mobile technologies offer the potential to reduce the costs of conducting clinical trials by collecting high-quality information on health outcomes in real-world settings that are relevant to patients and clinicians. However, widespread use of mobile technologies in clinical trials has been impeded by their perceived challenges. To advance solutions to these challenges, the Clinical Trials Transformation Initiative (CTTI) has issued best practices and realistic approaches that clinical trial sponsors can now use. These include CTTI recommendations on technology selection; data collection, analysis, and interpretation; data management; protocol design and execution; and US Food and Drug Administration submission and inspection. The scientific principles underpinning the clinical trials enterprise continue to apply to studies using mobile technologies. These recommendations provide a framework for including mobile technologies in clinical trials that can lead to more efficient assessment of new therapies for patients.","The authors of this publication have developed a set of guidelines for planning, running and writing up research that uses mobile technologies in clinical trials. The guidelines they have put together should make it easer for patient experience to be recorded in clinical trials.",doi:https://doi.org/10.1159/000503957; html:https://europepmc.org/articles/PMC7011727; pdf:https://europepmc.org/articles/PMC7011727?pdf=render; doi:https://doi.org/10.1159/000503957 34662334,https://doi.org/10.1371/journal.pgen.1009436,Machine learning to predict the source of campylobacteriosis using whole genome data.,"Arning N, Sheppard SK, Bayliss S, Clifton DA, Wilson DJ.",,PLoS genetics,2021,2021-10-18,Y,,,,"Campylobacteriosis is among the world's most common foodborne illnesses, caused predominantly by the bacterium Campylobacter jejuni. Effective interventions require determination of the infection source which is challenging as transmission occurs via multiple sources such as contaminated meat, poultry, and drinking water. Strain variation has allowed source tracking based upon allelic variation in multi-locus sequence typing (MLST) genes allowing isolates from infected individuals to be attributed to specific animal or environmental reservoirs. However, the accuracy of probabilistic attribution models has been limited by the ability to differentiate isolates based upon just 7 MLST genes. Here, we broaden the input data spectrum to include core genome MLST (cgMLST) and whole genome sequences (WGS), and implement multiple machine learning algorithms, allowing more accurate source attribution. We increase attribution accuracy from 64% using the standard iSource population genetic approach to 71% for MLST, 85% for cgMLST and 78% for kmerized WGS data using the classifier we named aiSource. To gain insight beyond the source model prediction, we use Bayesian inference to analyse the relative affinity of C. jejuni strains to infect humans and identified potential differences, in source-human transmission ability among clonally related isolates in the most common disease causing lineage (ST-21 clonal complex). Providing generalizable computationally efficient methods, based upon machine learning and population genetics, we provide a scalable approach to global disease surveillance that can continuously incorporate novel samples for source attribution and identify fine-scale variation in transmission potential.",,doi:https://doi.org/10.1371/journal.pgen.1009436; html:https://europepmc.org/articles/PMC8553134; pdf:https://europepmc.org/articles/PMC8553134?pdf=render; pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009436&type=printable -36258219,https://doi.org/10.1186/s13063-022-06824-6,"Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.","Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",,Trials,2022,2022-10-18,Y,,,,"

Aim

To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.

Methods and findings

During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab.

Conclusions

RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",,doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render 31408153,https://doi.org/10.1093/europace/euz220,"Subtypes of atrial fibrillation with concomitant valvular heart disease derived from electronic health records: phenotypes, population prevalence, trends and prognosis.","Banerjee A, Allan V, Denaxas S, Shah A, Kotecha D, Lambiase PD, Joseph J, Lund LH, Hemingway H.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2019,2019-12-01,Y,Mortality; Atrial fibrillation; Stroke; Valvular Heart Disease; Electronic Health Records; Systemic Embolism,The Human Phenome,,"

Aims

To evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.

Methods and results

A total of 76 019 individuals with AF were identified in England in 1998-2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02-1.24), 1.20 (1.05-1.36), and 1.27 (1.19-1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.

Conclusion

Prevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.","This study identified EHR records of AF and vavular heard disease in over 70k UK individuals and looked for associations with stroke, systemic embolism and mortality. They used CALIBER - a data source connecting office of national statistics, CPRD and HES data from over 10 years. They reported clear methodology on how the EHR was used to classify disease, showed overall prevalence change in different AF related diseases over time, and were able to provide insights at a more granular level - for example, valvular heart disease subtypes in AF than previous studies. The full code list (EHR codes) is provided in supplement, so methods are theoretically reproducible. Immediate impact to patient is less strong and there is wasn't much emphasis on diversity and inclusion.",doi:https://doi.org/10.1093/europace/euz220; html:https://europepmc.org/articles/PMC6888023; pdf:https://europepmc.org/articles/PMC6888023?pdf=render +36258219,https://doi.org/10.1186/s13063-022-06824-6,"Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.","Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",,Trials,2022,2022-10-18,Y,,,,"

Aim

To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.

Methods and findings

During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab.

Conclusions

RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",,doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render 31978332,https://doi.org/10.1016/j.ajhg.2020.01.003,A Multi-tissue Transcriptome Analysis of Human Metabolites Guides Interpretability of Associations Based on Multi-SNP Models for Gene Expression.,"Ndungu A, Payne A, Torres JM, van de Bunt M, McCarthy MI.",,American journal of human genetics,2020,2020-01-23,Y,Metabolites; Gene regulation; colocalization; Gene Expression; Gwas; Eqtls; Twas; S-predixcan; Multi-tissue Gtex; Transcriptome Wide Association Studies,,,"There is particular interest in transcriptome-wide association studies (TWAS) gene-level tests based on multi-SNP predictive models of gene expression-for identifying causal genes at loci associated with complex traits. However, interpretation of TWAS associations may be complicated by divergent effects of model SNPs on phenotype and gene expression. We developed an iterative modeling scheme for obtaining multi-SNP models of gene expression and applied this framework to generate expression models for 43 human tissues from the Genotype-Tissue Expression (GTEx) Project. We characterized the performance of single- and multi-SNP models for identifying causal genes in GWAS data for 46 circulating metabolites. We show that: (A) multi-SNP models captured more variation in expression than did the top cis-eQTL (median 2-fold improvement); (B) predicted expression based on multi-SNP models was associated (false discovery rate < 0.01) with metabolite levels for 826 unique gene-metabolite pairs, but, after stepwise conditional analyses, 90% were dominated by a single eQTL SNP; (C) among the 35% of associations where a SNP in the expression model was a significant cis-eQTL and metabolomic-QTL (met-QTL), 92% demonstrated colocalization between these signals, but interpretation was often complicated by incomplete overlap of QTLs in multi-SNP models; and (D) using a ""truth"" set of causal genes at 61 met-QTLs, the sensitivity was high (67%), but the positive predictive value was low, as only 8% of TWAS associations (19% when restricted to colocalized associations at met-QTLs) involved true causal genes. These results guide the interpretation of TWAS and highlight the need for corroborative data to provide confident assignment of causality.", ,doi:https://doi.org/10.1016/j.ajhg.2020.01.003; html:https://europepmc.org/articles/PMC7010967; pdf:https://europepmc.org/articles/PMC7010967?pdf=render 31678029,https://doi.org/10.1016/s1473-3099(19)30401-3,Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: an analysis of the Global Burden of Disease Study 2017.,GBD 2017 Diarrhoeal Disease Collaborators.,,The Lancet. Infectious diseases,2020,2019-10-31,Y,,,,"

Background

Many countries have shown marked declines in diarrhoeal disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017.

Methods

This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years.

Findings

Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78·4 deaths (70·1-87·1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69·6% (63·1-74·6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13·3% decrease, 11·2-15·5), childhood wasting (9·9% decrease, 9·6-10·2), and low use of oral rehydration solution (6·9% decrease, 4·8-8·4).

Interpretation

Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness.

Funding

Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S1473-3099(19)30401-3; html:https://europepmc.org/articles/PMC7340495 34561430,https://doi.org/10.1038/s41467-021-25703-3,Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.,"Schmidt AF, Hunt NB, Gordillo-Marañón M, Charoen P, Drenos F, Kivimaki M, Lawlor DA, Giambartolomei C, Papacosta O, Chaturvedi N, Bis JC, O'Donnell CJ, Wannamethee G, Wong A, Price JF, Hughes AD, Gaunt TR, Franceschini N, Mook-Kanamori DO, Zwierzyna M, Sofat R, Hingorani AD, Finan C.",,Nature communications,2021,2021-09-24,Y,,,,"Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.",,doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render @@ -2100,12 +2102,12 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 31477934,https://doi.org/10.1038/s41588-019-0483-y,Inferring whole-genome histories in large population datasets.,"Kelleher J, Wong Y, Wohns AW, Fadil C, Albers PK, McVean G.",,Nature genetics,2019,2019-09-02,Y,,The Human Phenome,,"Inferring the full genealogical history of a set of DNA sequences is a core problem in evolutionary biology, because this history encodes information about the events and forces that have influenced a species. However, current methods are limited, and the most accurate techniques are able to process no more than a hundred samples. As datasets that consist of millions of genomes are now being collected, there is a need for scalable and efficient inference methods to fully utilize these resources. Here we introduce an algorithm that is able to not only infer whole-genome histories with comparable accuracy to the state-of-the-art but also process four orders of magnitude more sequences. The approach also provides an 'evolutionary encoding' of the data, enabling efficient calculation of relevant statistics. We apply the method to human data from the 1000 Genomes Project, Simons Genome Diversity Project and UK Biobank, showing that the inferred genealogies are rich in biological signal and efficient to process.",,doi:https://doi.org/10.1038/s41588-019-0483-y; html:https://europepmc.org/articles/PMC6726478; pdf:https://europepmc.org/articles/PMC6726478?pdf=render 32732227,https://doi.org/10.1136/jmedgenet-2020-106922,Data-driven modelling of mutational hotspots and in silico predictors in hypertrophic cardiomyopathy.,"Waring A, Harper A, Salatino S, Kramer C, Neubauer S, Thomson K, Watkins H, Farrall M.",,Journal of medical genetics,2021,2020-07-30,Y,Genetics; Cardiomyopathy; Clinical Genetics,,,"

Background

Although rare missense variants in Mendelian disease genes often cluster in specific regions of proteins, it is unclear how to consider this when evaluating the pathogenicity of a gene or variant. Here we introduce methods for gene association and variant interpretation that use this powerful signal.

Methods

We present statistical methods to detect missense variant clustering (BIN-test) combined with burden information (ClusterBurden). We introduce a flexible generalised additive modelling (GAM) framework to identify mutational hotspots using burden and clustering information (hotspot model) and supplemented by in silico predictors (hotspot+ model). The methods were applied to synthetic data and a case-control dataset, comprising 5338 hypertrophic cardiomyopathy patients and 125 748 population reference samples over 34 putative cardiomyopathy genes.

Results

In simulations, the BIN-test was almost twice as powerful as the Anderson-Darling or Kolmogorov-Smirnov tests; ClusterBurden was computationally faster and more powerful than alternative position-informed methods. For 6/8 sarcomeric genes with strong clustering, Clusterburden showed enhanced power over burden-alone, equivalent to increasing the sample size by 50%. Hotspot+ models that combine burden, clustering and in silico predictors outperform generic pathogenicity predictors and effectively integrate ACMG criteria PM1 and PP3 to yield strong or moderate evidence of pathogenicity for 31.8% of examined variants of uncertain significance.

Conclusion

GAMs represent a unified statistical modelling framework to combine burden, clustering and functional information. Hotspot models can refine maps of regional burden and hotspot+ models can be powerful predictors of variant pathogenicity. The BIN-test is a fast powerful approach to detect missense variant clustering that when combined with burden information (ClusterBurden) may enhance disease-gene discovery.",,doi:https://doi.org/10.1136/jmedgenet-2020-106922; html:https://europepmc.org/articles/PMC8327322; pdf:https://europepmc.org/articles/PMC8327322?pdf=render 33495597,https://doi.org/10.1038/s41588-020-00764-0,Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.,"Harper AR, Goel A, Grace C, Thomson KL, Petersen SE, Xu X, Waring A, Ormondroyd E, Kramer CM, Ho CY, Neubauer S, HCMR Investigators, Tadros R, Ware JS, Bezzina CR, Farrall M, Watkins H.",,Nature genetics,2021,2021-01-25,N,,,,"Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h2g = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.",,doi:https://doi.org/10.1038/s41588-020-00764-0; html:https://europepmc.org/articles/PMC8240954; pdf:https://europepmc.org/articles/PMC8240954?pdf=render; doi:https://doi.org/10.1038/s41588-020-00764-0; pdf:https://openaccess.sgul.ac.uk/id/eprint/113790/1/EMS128763.pdf -36982069,https://doi.org/10.3390/ijerph20065161,The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.,"Lavalle R, Condominas E, Haro JM, Giné-Vázquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Peñarrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.",,International journal of environmental research and public health,2023,2023-03-15,Y,Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study,,,"The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the ""new normality"", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.",,doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render 29899974,https://doi.org/10.12688/f1000research.13830.2,Knowledge discovery for Deep Phenotyping serious mental illness from Electronic Mental Health records.,"Jackson R, Patel R, Velupillai S, Gkotsis G, Hoyle D, Stewart R.",,F1000Research,2018,2018-02-21,Y,Schizophrenia; Serious Mental Illness; Electronic Health Records; Natural Language Processing; Word2vec,,,"Background: Deep Phenotyping is the precise and comprehensive analysis of phenotypic features in which the individual components of the phenotype are observed and described. In UK mental health clinical practice, most clinically relevant information is recorded as free text in the Electronic Health Record, and offers a granularity of information beyond what is expressed in most medical knowledge bases. The SNOMED CT nomenclature potentially offers the means to model such information at scale, yet given a sufficiently large body of clinical text collected over many years, it is difficult to identify the language that clinicians favour to express concepts. Methods: By utilising a large corpus of healthcare data, we sought to make use of semantic modelling and clustering techniques to represent the relationship between the clinical vocabulary of internationally recognised SMI symptoms and the preferred language used by clinicians within a care setting. We explore how such models can be used for discovering novel vocabulary relevant to the task of phenotyping Serious Mental Illness (SMI) with only a small amount of prior knowledge.  Results: 20 403 terms were derived and curated via a two stage methodology. The list was reduced to 557 putative concepts based on eliminating redundant information content. These were then organised into 9 distinct categories pertaining to different aspects of psychiatric assessment. 235 concepts were found to be expressions of putative clinical significance. Of these, 53 were identified having novel synonymy with existing SNOMED CT concepts. 106 had no mapping to SNOMED CT. Conclusions: We demonstrate a scalable approach to discovering new concepts of SMI symptomatology based on real-world clinical observation. Such approaches may offer the opportunity to consider broader manifestations of SMI symptomatology than is typically assessed via current diagnostic frameworks, and create the potential for enhancing nomenclatures such as SNOMED CT based on real-world expressions.",,doi:https://doi.org/10.12688/f1000research.13830.2; html:https://europepmc.org/articles/PMC5968362; pdf:https://europepmc.org/articles/PMC5968362?pdf=render +36982069,https://doi.org/10.3390/ijerph20065161,The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.,"Lavalle R, Condominas E, Haro JM, Giné-Vázquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Peñarrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.",,International journal of environmental research and public health,2023,2023-03-15,Y,Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study,,,"The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the ""new normality"", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.",,doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render 33421867,https://doi.org/10.1016/j.jad.2020.12.053,Comorbidity of self-harm and disordered eating in young people: Evidence from a UK population-based cohort.,"Warne N, Heron J, Mars B, Moran P, Stewart A, Munafò M, Biddle L, Skinner A, Gunnell D, Bould H.",,Journal of affective disorders,2021,2021-01-07,Y,epidemiology; Self-harm; Comorbidity; Alspac; Disordered Eating,,,"

Background

Self-harm and eating disorders are often comorbid in clinical samples but their co-occurrence in the general population is unclear. Given that only a small proportion of individuals who self-harm or have disordered eating present to clinical services, and that both self-harm and eating disorders are associated with substantial morbidity and mortality, it is important to study these behaviours at a population level.

Methods

We assessed the co-occurrence of self-harm and disordered eating behaviours in 3384 females and 2326 males from a UK population-based cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants reported on their self-harm and disordered eating behaviours (fasting, purging, binge-eating and excessive exercise) in the last year via questionnaire at 16 and 24 years. At each age we assessed how many individuals who self-harm also reported disordered eating, and how many individuals with disordered eating also reported self-harm.

Results

We found high comorbidity of self-harm and disordered eating. Almost two-thirds of 16-year-old females, and two-in-five 24-year old males who self-harmed also reported some form of disordered eating. Young people with disordered eating reported higher levels of self-harm at both ages compared to those without disordered eating.

Limitations

We were not able to measure whether participants identified their disordered eating as a method of self-harm.

Conclusions

Self-harm and disordered eating commonly co-occur in young people in the general population. It is important to screen for both sets of difficulties to provide appropriate treatment.",,doi:https://doi.org/10.1016/j.jad.2020.12.053; html:https://europepmc.org/articles/PMC8150329 34090494,https://doi.org/10.1186/s13063-021-05284-8,A framework for handling missing accelerometer outcome data in trials.,"Tackney MS, Cook DG, Stahl D, Ismail K, Williamson E, Carpenter J.",,Trials,2021,2021-06-05,Y,Clinical Trial; Missing Data; Accelerometer; Multiple Imputation; Wearables,,,"Accelerometers and other wearable devices are increasingly being used in clinical trials to provide an objective measure of the impact of an intervention on physical activity. Missing data are ubiquitous in this setting, typically for one of two reasons: patients may not wear the device as per protocol, and/or the device may fail to collect data (e.g. flat battery, water damage). However, it is not always possible to distinguish whether the participant stopped wearing the device, or if the participant is wearing the device but staying still. Further, a lack of consensus in the literature on how to aggregate the data before analysis (hourly, daily, weekly) leads to a lack of consensus in how to define a ""missing"" outcome. Different trials have adopted different definitions (ranging from having insufficient step counts in a day, through to missing a certain number of days in a week). We propose an analysis framework that uses wear time to define missingness on the epoch and day level, and propose a multiple imputation approach, at the day level, which treats partially observed daily step counts as right censored. This flexible approach allows the inclusion of auxiliary variables, and is consistent with almost all the primary analysis models described in the literature, and readily allows sensitivity analysis (to the missing at random assumption) to be performed. Having presented our framework, we illustrate its application to the analysis of the 2019 MOVE-IT trial of motivational interviewing to increase exercise.",,doi:https://doi.org/10.1186/s13063-021-05284-8; html:https://europepmc.org/articles/PMC8178870; pdf:https://europepmc.org/articles/PMC8178870?pdf=render -33050951,https://doi.org/10.1186/s12916-020-01789-2,Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.,"van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.",,BMC medicine,2020,2020-10-14,Y,Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

We predicted median symptomatic attack rates over the first 12 months of 23% (Niger) to 42% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.

Conclusions

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.",,doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render 33420068,https://doi.org/10.1038/s41541-020-00267-3,Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines.,"Bahar MW, Porta C, Fox H, Macadam AJ, Fry EE, Stuart DI.",,NPJ vaccines,2021,2021-01-08,Y,,,,"Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.",,doi:https://doi.org/10.1038/s41541-020-00267-3; html:https://europepmc.org/articles/PMC7794334; pdf:https://europepmc.org/articles/PMC7794334?pdf=render +33050951,https://doi.org/10.1186/s12916-020-01789-2,Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.,"van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.",,BMC medicine,2020,2020-10-14,Y,Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

We predicted median symptomatic attack rates over the first 12 months of 23% (Niger) to 42% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.

Conclusions

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.",,doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render 34635854,https://doi.org/10.1038/s41591-021-01517-0,A quality assessment tool for artificial intelligence-centered diagnostic test accuracy studies: QUADAS-AI.,"Sounderajah V, Ashrafian H, Rose S, Shah NH, Ghassemi M, Golub R, Kahn CE, Esteva A, Karthikesalingam A, Mateen B, Webster D, Milea D, Ting D, Treanor D, Cushnan D, King D, McPherson D, Glocker B, Greaves F, Harling L, Ordish J, Cohen JF, Deeks J, Leeflang M, Diamond M, McInnes MDF, McCradden M, Abràmoff MD, Normahani P, Markar SR, Chang S, Liu X, Mallett S, Shetty S, Denniston A, Collins GS, Moher D, Whiting P, Bossuyt PM, Darzi A.",,Nature medicine,2021,2021-10-01,N,,,,,,doi:https://doi.org/10.1038/s41591-021-01517-0 33031764,https://doi.org/10.1016/s0140-6736(20)32013-4,"Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2020,2020-10-05,Y,,,,"

Background

Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092).

Interpretation

In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19.

Funding

Medical Research Council and National Institute for Health Research.",,doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623 30774489,https://doi.org/10.2147/prom.s162802,The use of patient-reported outcome research in modern ophthalmology: impact on clinical trials and routine clinical practice.,"Braithwaite T, Calvert M, Gray A, Pesudovs K, Denniston AK.",,Patient related outcome measures,2019,2019-01-24,Y,Randomized controlled trials; Eye Disease; Rasch Analysis; Patient-reported Outcome Measures,"Better, Faster and More Efficient Clinical Trials, The Human Phenome",,"This review article considers the rising demand for patient-reported outcome measures (PROMs) in modern ophthalmic research and clinical practice. We review what PROMs are, how they are developed and chosen for use, and how their quality can be critically appraised. We outline the progress made to develop PROMs in each clinical subspecialty. We highlight recent examples of the use of PROMs as secondary outcome measures in randomized controlled clinical trials and consider the impact they have had. With increasing interest in using PROMs as primary outcome measures, particularly where interventions have been found to be of equivalent efficacy by traditional outcome metrics, we highlight the importance of instrument precision in permitting smaller sample sizes to be recruited. Our review finds that while there has been considerable progress in PROM development, particularly in cataract, glaucoma, medical retina, and low vision, there is a paucity of useful tools for less common ophthalmic conditions. Development and validation of item banks, administered using computer adaptive testing, has been proposed as a solution to overcome many of the traditional limitations of PROMs, but further work will be needed to examine their acceptability to patients, clinicians, and investigators.",,doi:https://doi.org/10.2147/PROM.S162802; html:https://europepmc.org/articles/PMC6352858; pdf:https://europepmc.org/articles/PMC6352858?pdf=render @@ -2116,8 +2118,8 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 32384159,https://doi.org/10.1093/jtm/taaa068,Effectiveness of interventions targeting air travellers for delaying local outbreaks of SARS-CoV-2. ,"Clifford S, Pearson CAB, Klepac P, Van Zandvoort K, Quilty BJ, CMMID COVID-19 working group, Eggo RM, Flasche S.",,Journal of travel medicine,2020,2020-08-01,Y,,,,"We evaluated if interventions aimed at air travellers can delay local severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community transmission in a previously unaffected country. We simulated infected air travellers arriving into countries with no sustained SARS-CoV-2 transmission or other introduction routes from affected regions. We assessed the effectiveness of syndromic screening at departure and/or arrival and traveller sensitisation to the COVID-2019-like symptoms with the aim to trigger rapid self-isolation and reporting on symptom onset to enable contact tracing. We assumed that syndromic screening would reduce the number of infected arrivals and that traveller sensitisation reduces the average number of secondary cases. We use stochastic simulations to account for uncertainty in both arrival and secondary infections rates, and present sensitivity analyses on arrival rates of infected travellers and the effectiveness of traveller sensitisation. We report the median expected delay achievable in each scenario and an inner 50% interval. Under baseline assumptions, introducing exit and entry screening in combination with traveller sensitisation can delay a local SARS-CoV-2 outbreak by 8 days (50% interval: 3-14 days) when the rate of importation is 1 infected traveller per week at time of introduction. The additional benefit of entry screening is small if exit screening is effective: the combination of only exit screening and traveller sensitisation can delay an outbreak by 7 days (50% interval: 2-13 days). In the absence of screening, with less effective sensitisation, or a higher rate of importation, these delays shrink rapidly to <4 days. Syndromic screening and traveller sensitisation in combination may have marginally delayed SARS-CoV-2 outbreaks in unaffected countries.",,doi:https://doi.org/10.1093/jtm/taaa068; html:https://europepmc.org/articles/PMC7239177; pdf:https://europepmc.org/articles/PMC7239177?pdf=render 32855398,https://doi.org/10.1038/s41467-020-18060-0,Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases.,"Rabbie R, Ansari-Pour N, Cast O, Lau D, Scott F, Welsh SJ, Parkinson C, Khoja L, Moore L, Tullett M, Wong K, Ferreira I, Gómez JMM, Levesque M, Gallagher FA, Jiménez-Sánchez A, Riva L, Miller ML, Allinson K, Campbell PJ, Corrie P, Wedge DC, Adams DJ.",,Nature communications,2020,2020-08-27,Y,,,,"Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.",,doi:https://doi.org/10.1038/s41467-020-18060-0; html:https://europepmc.org/articles/PMC7453196; pdf:https://europepmc.org/articles/PMC7453196?pdf=render 35187482,https://doi.org/10.1093/braincomms/fcab291,Metabolic correlates of late midlife cognitive outcomes: findings from the 1946 British Birth Cohort.,"Green R, Lord J, Xu J, Maddock J, Kim M, Dobson R, Legido-Quigley C, Wong A, Richards M, Proitsi P.",,Brain communications,2022,2021-12-15,Y,Cognition; Dementia; Metabolomics; epidemiology; Network Analysis,,,"Investigating associations between metabolites and late midlife cognitive function could reveal potential markers and mechanisms relevant to early dementia. Here, we systematically explored the metabolic correlates of cognitive outcomes measured across the seventh decade of life, while untangling influencing life course factors. Using levels of 1019 metabolites profiled by liquid chromatography-mass spectrometry (age 60-64), we evaluated relationships between metabolites and cognitive outcomes in the British 1946 Birth Cohort (N = 1740). We additionally conducted pathway and network analyses to allow for greater insight into potential mechanisms, and sequentially adjusted for life course factors across four models, including sex and blood collection (Model 1), Model 1 + body mass index and lipid medication (Model 2), Model 2 + social factors and childhood cognition (Model 3) and Model 3 + lifestyle influences (Model 4). After adjusting for multiple tests, 155 metabolites, 10 pathways and 5 network modules were associated with cognitive outcomes. Of the 155, 35 metabolites were highly connected in their network module (termed 'hub' metabolites), presenting as promising marker candidates. Notably, we report relationships between a module comprised of acylcarnitines and processing speed which remained robust to life course adjustment, revealing palmitoylcarnitine (C16) as a hub (Model 4: β = -0.10, 95% confidence interval = -0.15 to -0.052, P = 5.99 × 10-5). Most associations were sensitive to adjustment for social factors and childhood cognition; in the final model, four metabolites remained after multiple testing correction, and 80 at P < 0.05. Two modules demonstrated associations that were partly or largely attenuated by life course factors: one enriched in modified nucleosides and amino acids (overall attenuation = 39.2-55.5%), and another in vitamin A and C metabolites (overall attenuation = 68.6-92.6%). Our other findings, including a module enriched in sphingolipid pathways, were entirely explained by life course factors, particularly childhood cognition and education. Using a large birth cohort study with information across the life course, we highlighted potential metabolic mechanisms associated with cognitive function in late midlife, suggesting marker candidates and life course relationships for further study.",,doi:https://doi.org/10.1093/braincomms/fcab291; html:https://europepmc.org/articles/PMC8853724; pdf:https://europepmc.org/articles/PMC8853724?pdf=render -35304391,https://doi.org/10.1136/bmjopen-2021-050610,Results of a pilot feasibility randomised controlled trial exploring the use of an electronic patient-reported outcome measure in the management of UK patients with advanced chronic kidney disease.,"Kyte D, Anderson N, Bishop J, Bissell A, Brettell E, Calvert M, Chadburn M, Cockwell P, Dutton M, Eddington H, Forster E, Hadley G, Ives NJ, Jackson LJ, O'Brien S, Price G, Sharpe K, Stringer S, Verdi R, Waters J, Wilcockson A.",,BMJ open,2022,2022-03-18,Y,Clinical Trials; Nephrology; End Stage Renal Failure,,,"

Objectives

The use of routine remote follow-up of patients with chronic kidney disease (CKD) is increasing exponentially. It has been suggested that online electronic patient-reported outcome measures (ePROMs) could be used in parallel, to facilitate real-time symptom monitoring aimed at improving outcomes. We tested the feasibility of this approach in a pilot trial of ePROM symptom monitoring versus usual care in patients with advanced CKD not on dialysis.

Design

A 12-month, parallel, pilot randomised controlled trial (RCT) and qualitative substudy.

Setting and participants

Queen Elizabeth Hospital Birmingham, UK. Adult patients with advanced CKD (estimated glomerular filtration rate ≥6 and ≤15 mL/min/1.73 m2, or a projected risk of progression to kidney failure within 2 years ≥20%).

Intervention

Monthly online ePROM symptom reporting, including automated feedback of tailored self-management advice and triggered clinical notifications in the advent of severe symptoms. Real-time ePROM data were made available to the clinical team via the electronic medical record.

Outcomes

Feasibility (recruitment and retention rates, and acceptability/adherence to the ePROM intervention). Health-related quality of life, clinical data (eg, measures of kidney function, kidney failure, hospitalisation, death) and healthcare utilisation.

Results

52 patients were randomised (31% of approached). Case report form returns were high (99.5%), as was retention (96%). Overall, 73% of expected ePROM questionnaires were received. Intervention adherence was high beyond 90 days (74%) and 180 days (65%); but dropped beyond 270 days (46%). Qualitative interviews supported proof of concept and intervention acceptability, but highlighted necessary changes aimed at enhancing overall functionality/scalability of the ePROM system.

Limitations

Small sample size.

Conclusions

This pilot trial demonstrates that patients are willing to be randomised to a trial assessing ePROM symptom monitoring. The intervention was considered acceptable; though measures to improve longer-term engagement are needed. A full-scale RCT is considered feasible.

Trial registration number

ISRCTN12669006 and the UK NIHR Portfolio (CPMS ID: 36497).",,doi:https://doi.org/10.1136/bmjopen-2021-050610; html:https://europepmc.org/articles/PMC8935185; pdf:https://europepmc.org/articles/PMC8935185?pdf=render 32543438,https://doi.org/10.1016/j.healthplace.2020.102355,Impact of air pollution on educational attainment for respiratory health treated students: A cross sectional data linkage study.,"Mizen A, Lyons J, Milojevic A, Doherty R, Wilkinson P, Carruthers D, Akbari A, Lake I, Davies GA, Al Sallakh M, Fry R, Dearden L, Rodgers SE.",,Health & place,2020,2020-05-12,Y,Air pollution; Asthma; poLLen; Data Linkage; Seasonal Allergic Rhinitis; Educational Attainment,,,"

Introduction

There is some evidence that exam results are worse when students are acutely exposed to air pollution. Studies investigating the association between air pollution and academic attainment have been constrained by small sample sizes.

Methods

Cross sectional educational attainment data (2009-2015) from students aged 15-16 years in Cardiff, Wales were linked to primary health care data, modelled air pollution and measured pollen data, and analysed using multilevel linear regression models. Annual cohort, school and individual level confounders were adjusted for in single and multi-pollutant/pollen models. We stratified by treatment of asthma and/or Seasonal Allergic Rhinitis (SAR).

Results

A unit (10μg/m3) increase of short-term exposure to NO2 was associated with 0.044 (95% CI: -0.079, -0.008) reduction of standardised Capped Point Score (CPS) after adjusting for individual and household risk factors for 18,241 students. This association remained statistically significant after controlling for other pollutants and pollen. There was no association of PM2.5, O3, or Pollen with standardised CPS remaining after adjustment. We found no evidence that treatment for asthma or SAR modified the observed NO2 effect on educational attainment.

Conclusion

Our study showed that short-term exposure to traffic-related air pollution, specifically NO2, was associated with detrimental educational attainment for students aged 15-16. Longitudinal investigations in different settings are required to confirm this possible impact and further work may uncover the long-term economic implications, and degree to which impacts are cumulative and permanent.",,doi:https://doi.org/10.1016/j.healthplace.2020.102355; html:https://europepmc.org/articles/PMC7214342 +35304391,https://doi.org/10.1136/bmjopen-2021-050610,Results of a pilot feasibility randomised controlled trial exploring the use of an electronic patient-reported outcome measure in the management of UK patients with advanced chronic kidney disease.,"Kyte D, Anderson N, Bishop J, Bissell A, Brettell E, Calvert M, Chadburn M, Cockwell P, Dutton M, Eddington H, Forster E, Hadley G, Ives NJ, Jackson LJ, O'Brien S, Price G, Sharpe K, Stringer S, Verdi R, Waters J, Wilcockson A.",,BMJ open,2022,2022-03-18,Y,Clinical Trials; Nephrology; End Stage Renal Failure,,,"

Objectives

The use of routine remote follow-up of patients with chronic kidney disease (CKD) is increasing exponentially. It has been suggested that online electronic patient-reported outcome measures (ePROMs) could be used in parallel, to facilitate real-time symptom monitoring aimed at improving outcomes. We tested the feasibility of this approach in a pilot trial of ePROM symptom monitoring versus usual care in patients with advanced CKD not on dialysis.

Design

A 12-month, parallel, pilot randomised controlled trial (RCT) and qualitative substudy.

Setting and participants

Queen Elizabeth Hospital Birmingham, UK. Adult patients with advanced CKD (estimated glomerular filtration rate ≥6 and ≤15 mL/min/1.73 m2, or a projected risk of progression to kidney failure within 2 years ≥20%).

Intervention

Monthly online ePROM symptom reporting, including automated feedback of tailored self-management advice and triggered clinical notifications in the advent of severe symptoms. Real-time ePROM data were made available to the clinical team via the electronic medical record.

Outcomes

Feasibility (recruitment and retention rates, and acceptability/adherence to the ePROM intervention). Health-related quality of life, clinical data (eg, measures of kidney function, kidney failure, hospitalisation, death) and healthcare utilisation.

Results

52 patients were randomised (31% of approached). Case report form returns were high (99.5%), as was retention (96%). Overall, 73% of expected ePROM questionnaires were received. Intervention adherence was high beyond 90 days (74%) and 180 days (65%); but dropped beyond 270 days (46%). Qualitative interviews supported proof of concept and intervention acceptability, but highlighted necessary changes aimed at enhancing overall functionality/scalability of the ePROM system.

Limitations

Small sample size.

Conclusions

This pilot trial demonstrates that patients are willing to be randomised to a trial assessing ePROM symptom monitoring. The intervention was considered acceptable; though measures to improve longer-term engagement are needed. A full-scale RCT is considered feasible.

Trial registration number

ISRCTN12669006 and the UK NIHR Portfolio (CPMS ID: 36497).",,doi:https://doi.org/10.1136/bmjopen-2021-050610; html:https://europepmc.org/articles/PMC8935185; pdf:https://europepmc.org/articles/PMC8935185?pdf=render 32376654,https://doi.org/10.1136/bmj.m1203,Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study.,"Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey Smith G.",,BMJ (Clinical research ed.),2020,2020-05-06,Y,,,,"

Objective

To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood.

Design

Two sample univariable and multivariable mendelian randomisation.

Setting

The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums.

Participants

453 169 participants enrolled in UK Biobank and a combined total of more than 700 000 people from different GWAS consortiums.

Exposures

Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10.

Main outcome measures

Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer.

Results

Having a larger genetically predicted body size in early life was associated with an increased odds of coronary artery disease (odds ratio 1.49 for each change in body size category unless stated otherwise, 95% confidence interval 1.33 to 1.68) and type 2 diabetes (2.32, 1.76 to 3.05) based on univariable mendelian randomisation analyses. However, little evidence was found of a direct effect (ie, not through adult body size) based on multivariable mendelian randomisation estimates (coronary artery disease: 1.02, 0.86 to 1.22; type 2 diabetes:1.16, 0.74 to 1.82). In the multivariable mendelian randomisation analysis of breast cancer risk, strong evidence was found of a protective direct effect for larger body size in early life (0.59, 0.50 to 0.71), with less evidence of a direct effect of adult body size on this outcome (1.08, 0.93 to 1.27). Including age at menarche as an additional exposure provided weak evidence of a total causal effect (univariable mendelian randomisation odds ratio 0.98, 95% confidence interval 0.91 to 1.06) but strong evidence of a direct causal effect, independent of early life and adult body size (multivariable mendelian randomisation odds ratio 0.90, 0.85 to 0.95). No strong evidence was found of a causal effect of either early or later life measures on prostate cancer (early life body size odds ratio 1.06, 95% confidence interval 0.81 to 1.40; adult body size 0.87, 0.70 to 1.08).

Conclusions

The findings suggest that the positive association between body size in childhood and risk of coronary artery disease and type 2 diabetes in adulthood can be attributed to individuals remaining large into later life. However, having a smaller body size during childhood might increase the risk of breast cancer regardless of body size in adulthood, with timing of puberty also putatively playing a role.",,doi:https://doi.org/10.1136/bmj.m1203; html:https://europepmc.org/articles/PMC7201936 33830302,https://doi.org/10.1007/s00125-021-05428-0,Analysis of overlapping genetic association in type 1 and type 2 diabetes.,"Inshaw JRJ, Sidore C, Cucca F, Stefana MI, Crouch DJM, McCarthy MI, Mahajan A, Todd JA.",,Diabetologia,2021,2021-04-08,Y,Genetics; Insulin; Systematic; Statistics; Type 2 diabetes; type 1 diabetes; Analyses; Genome-wide Association Study; Co-localisation,,,"

Aims/hypothesis

Given the potential shared aetiology between type 1 and type 2 diabetes, we aimed to identify any genetic regions associated with both diseases. For associations where there is a shared signal and the allele that increases risk to one disease also increases risk to the other, inference about shared aetiology could be made, with the potential to develop therapeutic strategies to treat or prevent both diseases simultaneously. Alternatively, if a genetic signal co-localises with divergent effect directions, it could provide valuable biological insight into how the association affects the two diseases differently.

Methods

Using publicly available type 2 diabetes summary statistics from a genome-wide association study (GWAS) meta-analysis of European ancestry individuals (74,124 cases and 824,006 controls) and type 1 diabetes GWAS summary statistics from a meta-analysis of studies on individuals from the UK and Sardinia (7467 cases and 10,218 controls), we identified all regions of 0.5 Mb that contained variants associated with both diseases (false discovery rate <0.01). In each region, we performed forward stepwise logistic regression to identify independent association signals, then examined co-localisation of each type 1 diabetes signal with each type 2 diabetes signal using coloc. Any association with a co-localisation posterior probability of ≥0.9 was considered a genuine shared association with both diseases.

Results

Of the 81 association signals from 42 genetic regions that showed association with both type 1 and type 2 diabetes, four association signals co-localised between both diseases (posterior probability ≥0.9): (1) chromosome 16q23.1, near CTRB1/BCAR1, which has been previously identified; (2) chromosome 11p15.5, near the INS gene; (3) chromosome 4p16.3, near TMEM129 and (4) chromosome 1p31.3, near PGM1. In each of these regions, the effect of genetic variants on type 1 diabetes was in the opposite direction to the effect on type 2 diabetes. Use of additional datasets also supported the previously identified co-localisation on chromosome 9p24.2, near the GLIS3 gene, in this case with a concordant direction of effect.

Conclusions/interpretation

Four of five association signals that co-localise between type 1 diabetes and type 2 diabetes are in opposite directions, suggesting a complex genetic relationship between the two diseases.",,doi:https://doi.org/10.1007/s00125-021-05428-0; html:https://europepmc.org/articles/PMC8099827; pdf:https://europepmc.org/articles/PMC8099827?pdf=render 36210437,https://doi.org/10.1186/s12916-022-02588-7,Hesitancy for receiving regular SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis from the UK-REACH study.,"Veli N, Martin CA, Woolf K, Nazareth J, Pan D, Al-Oraibi A, Baggaley RF, Bryant L, Nellums LB, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,BMC medicine,2022,2022-10-10,Y,Vaccination; Ethnicity; Healthcare; Hesitancy; Covid-19; Sars-cov-2,,,"

Background

Regular vaccination against SARS-CoV-2 may be needed to maintain immunity in 'at-risk' populations, which include healthcare workers (HCWs). However, little is known about the proportion of HCWs who might be hesitant about receiving a hypothetical regular SARS-CoV-2 vaccination or the factors associated with this hesitancy.

Methods

Cross-sectional analysis of questionnaire data collected as part of UK-REACH, a nationwide, longitudinal cohort study of HCWs. The outcome measure was binary, either a participant indicated they would definitely accept regular SARS-CoV-2 vaccination if recommended or they indicated some degree of hesitancy regarding acceptance (probably accept or less likely). We used logistic regression to identify factors associated with hesitancy for receiving regular vaccination.

Results

A total of 5454 HCWs were included in the analysed cohort, 23.5% of whom were hesitant about regular SARS-CoV-2 vaccination. Black HCWs were more likely to be hesitant than White HCWs (aOR 2.60, 95%CI 1.80-3.72) as were those who reported a previous episode of COVID-19 (1.33, 1.13-1.57 [vs those who tested negative]). Those who received influenza vaccination in the previous two seasons were over five times less likely to report hesitancy for regular SARS-CoV-2 vaccination than those not vaccinated against influenza in either season (0.18, 0.14-0.21). HCWs who trusted official sources of vaccine information (such as NHS or government adverts or websites) were less likely to report hesitancy for a regular vaccination programme. Those who had been exposed to information advocating against vaccination from friends and family were more likely to be hesitant.

Conclusions

In this study, nearly a quarter of UK HCWs were hesitant about receiving a regular SARS-CoV-2 vaccination. We have identified key factors associated with hesitancy for regular SARS-CoV-2 vaccination, which can be used to identify groups of HCWs at the highest risk of vaccine hesitancy and tailor interventions accordingly. Family and friends of HCWs may influence decisions about regular vaccination. This implies that working with HCWs and their social networks to allay concerns about SARS-CoV-2 vaccination could improve uptake in a regular vaccination programme.

Trial registration

ISRCTN Registry, ISRCTN11811602.",,doi:https://doi.org/10.1186/s12916-022-02588-7; html:https://europepmc.org/articles/PMC9548389; pdf:https://europepmc.org/articles/PMC9548389?pdf=render @@ -2168,8 +2170,8 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 36065116,https://doi.org/10.1093/brain/awac321,Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.,"Needham EJ, Ren AL, Digby RJ, Norton EJ, Ebrahimi S, Outtrim JG, Chatfield DA, Manktelow AE, Leibowitz MM, Newcombe VFJ, Doffinger R, Barcenas-Morales G, Fonseca C, Taussig MJ, Burnstein RM, Samanta RJ, Dunai C, Sithole N, Ashton NJ, Zetterberg H, Gisslén M, Edén A, Marklund E, Openshaw PJM, Dunning J, Griffiths MJ, Cavanagh J, Breen G, Irani SR, Elmer A, Kingston N, Summers C, Bradley JR, Taams LS, Michael BD, Bullmore ET, Smith KGC, Lyons PA, Coles AJ, Menon DK, Cambridge NeuroCOVID Group, CITIID-NIHR COVID-19 BioResource Collaboration, Cambridge NIHR Clinical Research Facility.",,Brain : a journal of neurology,2022,2022-11-01,Y,Autoantibodies; Brain injury; neuroinflammation; Covid-19,,,"COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.",,doi:https://doi.org/10.1093/brain/awac321; html:https://europepmc.org/articles/PMC9494359; pdf:https://europepmc.org/articles/PMC9494359?pdf=render; pdf:https://academic.oup.com/brain/article-pdf/145/11/4097/47170622/awac321.pdf 30941398,https://doi.org/10.1093/aje/kwz090,Determinants of Transmission Risk During the Late Stage of the West African Ebola Epidemic.,"Robert A, Edmunds WJ, Watson CH, Henao-Restrepo AM, Gsell PS, Williamson E, Longini IM, Sakoba K, Kucharski AJ, Touré A, Nadlaou SD, Diallo B, Barry MS, Fofana TO, Camara L, Kaba IL, Sylla L, Diaby ML, Soumah O, Diallo A, Niare A, Diallo A, Eggo RM.",,American journal of epidemiology,2019,2019-07-01,Y,Regression analysis; Guinea; risk factors; Multiple Imputation; Ebola,"Applied Analytics, Improving Public Health",,"Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013-2016 Ebola epidemic in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola treatment unit was associated with a 38% decrease in secondary cases (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI): 0.38, 0.99) among individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR = 1.82, 95% CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77) compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR = 0.35, 95% CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR = 0.71, 95% CI: 0.55, 0.93). This detailed surveillance data set provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD.",,doi:https://doi.org/10.1093/aje/kwz090; html:https://europepmc.org/articles/PMC6601535; pdf:https://europepmc.org/articles/PMC6601535?pdf=render 34098341,https://doi.org/10.1016/j.ebiom.2021.103414,Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study.,"Jones HE, Mulchandani R, Taylor-Phillips S, Ades AE, Shute J, Perry KR, Chandra NL, Brooks T, Charlett A, Hickman M, Oliver I, Kaptoge S, Danesh J, Di Angelantonio E, Wyllie D, COMPARE study investigators, EDSAB-HOME investigators.",,EBioMedicine,2021,2021-06-04,Y,Seroepidemiology; Rapid Testing; Serosurveillance; Lateral Flow Devices; Covid-19,,,"

Background

SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy.

Methods

In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices.

Findings

We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19TM device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations (""spectrum effects""), but the extent of this varied by device.

Interpretation

The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives.

Funding

Public Health England.",,doi:https://doi.org/10.1016/j.ebiom.2021.103414; html:https://europepmc.org/articles/PMC8176919; pdf:https://europepmc.org/articles/PMC8176919?pdf=render -33536631,https://doi.org/10.1038/s42003-020-01575-z,A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.,"Bell S, Rigas AS, Magnusson MK, Ferkingstad E, Allara E, Bjornsdottir G, Ramond A, Sørensen E, Halldorsson GH, Paul DS, Burgdorf KS, Eggertsson HP, Howson JMM, Thørner LW, Kristmundsdottir S, Astle WJ, Erikstrup C, Sigurdsson JK, Vuckovic D, Dinh KM, Tragante V, Surendran P, Pedersen OB, Vidarsson B, Jiang T, Paarup HM, Onundarson PT, Akbari P, Nielsen KR, Lund SH, Juliusson K, Magnusson MI, Frigge ML, Oddsson A, Olafsson I, Kaptoge S, Hjalgrim H, Runarsson G, Wood AM, Jonsdottir I, Hansen TF, Sigurdardottir O, Stefansson H, Rye D, DBDS Genomic Consortium, Peters JE, Westergaard D, Holm H, Soranzo N, Banasik K, Thorleifsson G, Ouwehand WH, Thorsteinsdottir U, Roberts DJ, Sulem P, Butterworth AS, Gudbjartsson DF, Danesh J, Brunak S, Di Angelantonio E, Ullum H, Stefansson K.",,Communications biology,2021,2021-02-03,Y,,,,"Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.",,doi:https://doi.org/10.1038/s42003-020-01575-z; html:https://europepmc.org/articles/PMC7859200; pdf:https://europepmc.org/articles/PMC7859200?pdf=render 33737413,https://doi.org/10.1136/bmj.n628,Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England.,"Forbes H, Morton CE, Bacon S, McDonald HI, Minassian C, Brown JP, Rentsch CT, Mathur R, Schultze A, DeVito NJ, MacKenna B, Hulme WJ, Croker R, Walker AJ, Williamson EJ, Bates C, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Drysdale H, Wong AYS, Cockburn J, McManus R, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Evans SJW, Bhaskaran K, Eggo RM, Goldacre B, Tomlinson LA.",,BMJ (Clinical research ed.),2021,2021-03-18,Y,,,,"

Objective

To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic.

Design

Population based cohort study, on behalf of NHS England.

Setting

Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020).

Participants

Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020.

Main outcome measures

Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household.

Results

Among 9 334 392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or intensive care admission, or death from covid-19. In wave 2, among adults aged 65 years and under, living with children of any age was associated with an increased risk of recorded SARS-CoV-2 infection (hazard ratio 1.06 (95% confidence interval 1.05 to 1.08) for living with children aged 0-11 years; 1.22 (1.20 to 1.24) for living with children aged 12-18 years) and covid-19 related hospital admission (1.18 (1.06 to 1.31) for living with children aged 0-11; 1.26 (1.12 to 1.40) for living with children aged 12-18). Living with children aged 0-11 was associated with reduced risk of death from both covid-19 and non-covid-19 causes in both waves; living with children of any age was also associated with lower risk of dying from non-covid-19 causes. For adults 65 years and under during wave 2, living with children aged 0-11 years was associated with an increased absolute risk of having SARS-CoV-2 infection recorded of 40-60 per 10 000 people, from 810 to between 850 and 870, and an increase in the number of hospital admissions of 1-5 per 10 000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10 000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10 000 in the number of hospital admissions.

Conclusions

In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.",,doi:https://doi.org/10.1136/bmj.n628; html:https://europepmc.org/articles/PMC7970340; pdf:https://europepmc.org/articles/PMC7970340?pdf=render; pdf:https://www.bmj.com/content/bmj/372/bmj.n628.full.pdf +33536631,https://doi.org/10.1038/s42003-020-01575-z,A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.,"Bell S, Rigas AS, Magnusson MK, Ferkingstad E, Allara E, Bjornsdottir G, Ramond A, Sørensen E, Halldorsson GH, Paul DS, Burgdorf KS, Eggertsson HP, Howson JMM, Thørner LW, Kristmundsdottir S, Astle WJ, Erikstrup C, Sigurdsson JK, Vuckovic D, Dinh KM, Tragante V, Surendran P, Pedersen OB, Vidarsson B, Jiang T, Paarup HM, Onundarson PT, Akbari P, Nielsen KR, Lund SH, Juliusson K, Magnusson MI, Frigge ML, Oddsson A, Olafsson I, Kaptoge S, Hjalgrim H, Runarsson G, Wood AM, Jonsdottir I, Hansen TF, Sigurdardottir O, Stefansson H, Rye D, DBDS Genomic Consortium, Peters JE, Westergaard D, Holm H, Soranzo N, Banasik K, Thorleifsson G, Ouwehand WH, Thorsteinsdottir U, Roberts DJ, Sulem P, Butterworth AS, Gudbjartsson DF, Danesh J, Brunak S, Di Angelantonio E, Ullum H, Stefansson K.",,Communications biology,2021,2021-02-03,Y,,,,"Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.",,doi:https://doi.org/10.1038/s42003-020-01575-z; html:https://europepmc.org/articles/PMC7859200; pdf:https://europepmc.org/articles/PMC7859200?pdf=render 30814958,https://doi.org/10.3389/fpsyt.2019.00036,Risk Assessment Tools and Data-Driven Approaches for Predicting and Preventing Suicidal Behavior.,"Velupillai S, Hadlaczky G, Baca-Garcia E, Gorrell GM, Werbeloff N, Nguyen D, Patel R, Leightley D, Downs J, Hotopf M, Dutta R.",,Frontiers in psychiatry,2019,2019-02-13,Y,Machine Learning; Suicidality; Natural Language Processing; Clinical Informatics; Suicide Risk Assessment; Suicide Risk Prediction,Applied Analytics,,"Risk assessment of suicidal behavior is a time-consuming but notoriously inaccurate activity for mental health services globally. In the last 50 years a large number of tools have been designed for suicide risk assessment, and tested in a wide variety of populations, but studies show that these tools suffer from low positive predictive values. More recently, advances in research fields such as machine learning and natural language processing applied on large datasets have shown promising results for health care, and may enable an important shift in advancing precision medicine. In this conceptual review, we discuss established risk assessment tools and examples of novel data-driven approaches that have been used for identification of suicidal behavior and risk. We provide a perspective on the strengths and weaknesses of these applications to mental health-related data, and suggest research directions to enable improvement in clinical practice.",,doi:https://doi.org/10.3389/fpsyt.2019.00036; html:https://europepmc.org/articles/PMC6381841; pdf:https://europepmc.org/articles/PMC6381841?pdf=render 34051920,https://doi.org/10.1016/s2468-2667(21)00065-7,"Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019.",GBD 2019 Chewing Tobacco Collaborators.,,The Lancet. Public health,2021,2021-05-28,Y,,,,"

Background

Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control.

Methods

We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period.

Findings

In 2019, 273·9 million (95% uncertainty interval 258·5 to 290·9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4·72% (4·46 to 5·01). 228·2 million (213·6 to 244·7; 83·29% [82·15 to 84·42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age-standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1·21% [-1·26 to -1·16]), similar progress was not observed for chewing tobacco (0·46% [0·13 to 0·79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0·94% [-1·72 to -0·14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period.

Interpretation

Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence.

Funding

Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2468-2667(21)00065-7; html:https://europepmc.org/articles/PMC8251505; pdf:http://www.thelancet.com/article/S2468266721000657/pdf 32207686,https://doi.org/10.7554/elife.54363,Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria. ,"McGregor TL, Hunt KA, Yee E, Mason D, Nioi P, Ticau S, Pelosi M, Loken PR, Finer S, Lawlor DA, Fauman EB, Huang QQ, Griffiths CJ, MacArthur DG, Trembath RC, Oglesbee D, Lieske JC, Erbe DV, Wright J, van Heel DA.",,eLife,2020,2020-03-24,Y,,Understanding the Causes of Disease,metabolic and endocrine,"By sequencing autozygous human populations, we identified a healthy adult woman with lifelong complete knockout of HAO1 (expected ~1 in 30 million outbred people). HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n = 67). Plasma metabolomics and lipidomics (1871 biochemicals) revealed 18 markedly elevated biochemicals (>5 sd outliers versus n = 25 controls) suggesting additional HAO1 effects. Comparison with lumasiran preclinical and clinical trial data suggested she has <2% residual glycolate oxidase activity. Cell line p.Leu333SerfsTer4 expression showed markedly reduced HAO1 protein levels and cellular protein mis-localisation. In this woman, lifelong HAO1 knockout is safe and without clinical phenotype, de-risking a therapeutic approach and informing therapeutic mechanisms. Unlocking evidence from the diversity of human genetic variation can facilitate drug development.",,doi:https://doi.org/10.7554/eLife.54363; html:https://europepmc.org/articles/PMC7108859; pdf:https://europepmc.org/articles/PMC7108859?pdf=render @@ -2219,8 +2221,8 @@ PMC10435379,https://doi.org/,Genotyping and population characteristics of the Ch 34582791,https://doi.org/10.1016/j.ajhg.2021.08.007,Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program.,"Mikhaylova AV, McHugh CP, Polfus LM, Raffield LM, Boorgula MP, Blackwell TW, Brody JA, Broome J, Chami N, Chen MH, Conomos MP, Cox C, Curran JE, Daya M, Ekunwe L, Glahn DC, Heard-Costa N, Highland HM, Hobbs BD, Ilboudo Y, Jain D, Lange LA, Miller-Fleming TW, Min N, Moon JY, Preuss MH, Rosen J, Ryan K, Smith AV, Sun Q, Surendran P, de Vries PS, Walter K, Wang Z, Wheeler M, Yanek LR, Zhong X, Abecasis GR, Almasy L, Barnes KC, Beaty TH, Becker LC, Blangero J, Boerwinkle E, Butterworth AS, Chavan S, Cho MH, Choquet H, Correa A, Cox N, DeMeo DL, Faraday N, Fornage M, Gerszten RE, Hou L, Johnson AD, Jorgenson E, Kaplan R, Kooperberg C, Kundu K, Laurie CA, Lettre G, Lewis JP, Li B, Li Y, Lloyd-Jones DM, Loos RJF, Manichaikul A, Meyers DA, Mitchell BD, Morrison AC, Ngo D, Nickerson DA, Nongmaithem S, North KE, O'Connell JR, Ortega VE, Pankratz N, Perry JA, Psaty BM, Rich SS, Soranzo N, Rotter JI, Silverman EK, Smith NL, Tang H, Tracy RP, Thornton TA, Vasan RS, Zein J, Mathias RA, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Reiner AP, Auer PL.",,American journal of human genetics,2021,2021-09-27,N,Whole-genome Sequencing; Blood-cell Counts,,,"Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs.",,doi:https://doi.org/10.1016/j.ajhg.2021.08.007; html:https://europepmc.org/articles/PMC8546043; pdf:https://europepmc.org/articles/PMC8546043?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2021.08.007 34083753,https://doi.org/10.1038/s41562-021-01108-6,"Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000-2018.","Bhattacharjee NV, Schaeffer LE, Hay SI, Local Burden of Disease Exclusive Breastfeeding Collaborators.",,Nature human behaviour,2021,2021-06-03,Y,,,,"Exclusive breastfeeding (EBF)-giving infants only breast-milk for the first 6 months of life-is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization's Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.",,doi:https://doi.org/10.1038/s41562-021-01108-6; html:https://europepmc.org/articles/PMC8373614; pdf:https://europepmc.org/articles/PMC8373614?pdf=render; pdf:https://www.nature.com/articles/s41562-021-01108-6.pdf 33495596,https://doi.org/10.1038/s41588-020-00762-2,Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect. ,"Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, Kelu Bisabu K, Walsh R, Hoorntje ET, Te Rijdt WP, Buchan RJ, van Velzen HG, van Slegtenhorst MA, Vermeulen JM, Offerhaus JA, Bai W, de Marvao A, Lahrouchi N, Beekman L, Karper JC, Veldink JH, Kayvanpour E, Pantazis A, Baksi AJ, Whiffin N, Mazzarotto F, Sloane G, Suzuki H, Schneider-Luftman D, Elliott P, Richard P, Ader F, Villard E, Lichtner P, Meitinger T, Tanck MWT, van Tintelen JP, Thain A, McCarty D, Hegele RA, Roberts JD, Amyot J, Dubé MP, Cadrin-Tourigny J, Giraldeau G, L'Allier PL, Garceau P, Tardif JC, Boekholdt SM, Lumbers RT, Asselbergs FW, Barton PJR, Cook SA, Prasad SK, O'Regan DP, van der Velden J, Verweij KJH, Talajic M, Lettre G, Pinto YM, Meder B, Charron P, de Boer RA, Christiaans I, Michels M, Wilde AAM, Watkins H, Matthews PM, Ware JS, Bezzina CR.",,Nature genetics,2021,2021-01-25,Y,,,,"The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.",,doi:https://doi.org/10.1038/s41588-020-00762-2; html:https://europepmc.org/articles/PMC7611259; pdf:https://europepmc.org/articles/PMC7611259?pdf=render; pdf:https://europepmc.org/articles/pmc7611259?pdf=render -35013731,https://doi.org/10.1016/j.lanepe.2021.100299,Persistent hesitancy for SARS-CoV-2 vaccines among healthcare workers in the United Kingdom: analysis of longitudinal data from the UK-REACH cohort study.,"Martin CA, Woolf K, Bryant L, Carr S, Gray LJ, Gupta A, Guyatt AL, John C, Melbourne C, McManus IC, Nazareth J, Nellums LB, Tobin MD, Pan D, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2022,2022-01-04,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2021.100299; html:https://europepmc.org/articles/PMC8730737; pdf:https://europepmc.org/articles/PMC8730737?pdf=render 34773122,https://doi.org/10.1038/s41588-021-00977-x,"Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.","Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, Rongve A, Børte S, Winsvold BS, Drange OK, Martinsen AE, Skogholt AH, Willer C, Bråthen G, Bosnes I, Nielsen JB, Fritsche LG, Thomas LF, Pedersen LM, Gabrielsen ME, Johnsen MB, Meisingset TW, Zhou W, Proitsi P, Hodges A, Dobson R, Velayudhan L, Heilbron K, Auton A, 23andMe Research Team, Sealock JM, Davis LK, Pedersen NL, Reynolds CA, Karlsson IK, Magnusson S, Stefansson H, Thordardottir S, Jonsson PV, Snaedal J, Zettergren A, Skoog I, Kern S, Waern M, Zetterberg H, Blennow K, Stordal E, Hveem K, Zwart JA, Athanasiu L, Selnes P, Saltvedt I, Sando SB, Ulstein I, Djurovic S, Fladby T, Aarsland D, Selbæk G, Ripke S, Stefansson K, Andreassen OA, Posthuma D.",,Nature genetics,2021,2021-12-01,N,,,,,,doi:https://doi.org/10.1038/s41588-021-00977-x +35013731,https://doi.org/10.1016/j.lanepe.2021.100299,Persistent hesitancy for SARS-CoV-2 vaccines among healthcare workers in the United Kingdom: analysis of longitudinal data from the UK-REACH cohort study.,"Martin CA, Woolf K, Bryant L, Carr S, Gray LJ, Gupta A, Guyatt AL, John C, Melbourne C, McManus IC, Nazareth J, Nellums LB, Tobin MD, Pan D, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2022,2022-01-04,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2021.100299; html:https://europepmc.org/articles/PMC8730737; pdf:https://europepmc.org/articles/PMC8730737?pdf=render 32573913,https://doi.org/10.1002/alz.12106,Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways.,"Sherva R, Gross A, Mukherjee S, Koesterer R, Amouyel P, Bellenguez C, Dufouil C, Bennett DA, Chibnik L, Cruchaga C, Del-Aguila J, Farrer LA, Mayeux R, Munsie L, Winslow A, Newhouse S, Saykin AJ, Kauwe JSK, Alzheimer's Disease Genetics Consortium, Crane PK, Green RC.",,Alzheimer's & dementia : the journal of the Alzheimer's Association,2020,2020-06-23,N,Disease Progression; Genetic Association; Cognitive Decline; Pathway analysis,,,"

Introduction

Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome-wide association study to examine rate of cognitive decline (ROD) in patients with AD.

Methods

We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes.

Results

Suggestive associations (P < 1.0 × 10-6 ) were observed on chromosome 15 in DNA polymerase-γ (rs3176205, P = 1.11 × 10-7 ), chromosome 7 (rs60465337,P = 4.06 × 10-7 ) in contactin-associated protein-2, in RP11-384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10-7 ), family with sequence similarity 214 member-A on chromosome 15 (rs2899492, P = 5.94 × 10-7 ), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10-7 ) and 4 (rs1304013, P = 7.73 × 10-7 ). Significant pathways involving neuronal development and function, apoptosis, memory, and inflammation were identified.

Discussion

Pathways related to AD, intelligence, and neurological function determine AD progression, while previously identified AD risk variants, including the apolipoprotein (APOE) ε4 and ε2 variants, do not have a major impact.",,doi:https://doi.org/10.1002/alz.12106; html:https://europepmc.org/articles/PMC7924136; pdf:https://europepmc.org/articles/PMC7924136?pdf=render; doi:https://doi.org/10.1002/alz.12106 34667060,https://doi.org/10.1183/13993003.02730-2021,Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. ,"Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet LP.",,The European respiratory journal,2022,2021-12-31,Y,,,,,,doi:https://doi.org/10.1183/13993003.02730-2021; html:https://europepmc.org/articles/PMC8719459; pdf:https://europepmc.org/articles/PMC8719459?pdf=render 35072136,https://doi.org/10.1016/j.xgen.2021.100029,GA4GH: International policies and standards for data sharing across genomic research and healthcare.,"Rehm HL, Page AJH, Smith L, Adams JB, Alterovitz G, Babb LJ, Barkley MP, Baudis M, Beauvais MJS, Beck T, Beckmann JS, Beltran S, Bernick D, Bernier A, Bonfield JK, Boughtwood TF, Bourque G, Bowers SR, Brookes AJ, Brudno M, Brush MH, Bujold D, Burdett T, Buske OJ, Cabili MN, Cameron DL, Carroll RJ, Casas-Silva E, Chakravarty D, Chaudhari BP, Chen SH, Cherry JM, Chung J, Cline M, Clissold HL, Cook-Deegan RM, Courtot M, Cunningham F, Cupak M, Davies RM, Denisko D, Doerr MJ, Dolman LI, Dove ES, Dursi LJ, Dyke SOM, Eddy JA, Eilbeck K, Ellrott KP, Fairley S, Fakhro KA, Firth HV, Fitzsimons MS, Fiume M, Flicek P, Fore IM, Freeberg MA, Freimuth RR, Fromont LA, Fuerth J, Gaff CL, Gan W, Ghanaim EM, Glazer D, Green RC, Griffith M, Griffith OL, Grossman RL, Groza T, Auvil JMG, Guigó R, Gupta D, Haendel MA, Hamosh A, Hansen DP, Hart RK, Hartley DM, Haussler D, Hendricks-Sturrup RM, Ho CWL, Hobb AE, Hoffman MM, Hofmann OM, Holub P, Hsu JS, Hubaux JP, Hunt SE, Husami A, Jacobsen JO, Jamuar SS, Janes EL, Jeanson F, Jené A, Johns AL, Joly Y, Jones SJM, Kanitz A, Kato K, Keane TM, Kekesi-Lafrance K, Kelleher J, Kerry G, Khor SS, Knoppers BM, Konopko MA, Kosaki K, Kuba M, Lawson J, Leinonen R, Li S, Lin MF, Linden M, Liu X, Udara Liyanage I, Lopez J, Lucassen AM, Lukowski M, Mann AL, Marshall J, Mattioni M, Metke-Jimenez A, Middleton A, Milne RJ, Molnár-Gábor F, Mulder N, Munoz-Torres MC, Nag R, Nakagawa H, Nasir J, Navarro A, Nelson TH, Niewielska A, Nisselle A, Niu J, Nyrönen TH, O'Connor BD, Oesterle S, Ogishima S, Wang VO, Paglione LAD, Palumbo E, Parkinson HE, Philippakis AA, Pizarro AD, Prlic A, Rambla J, Rendon A, Rider RA, Robinson PN, Rodarmer KW, Rodriguez LL, Rubin AF, Rueda M, Rushton GA, Ryan RS, Saunders GI, Schuilenburg H, Schwede T, Scollen S, Senf A, Sheffield NC, Skantharajah N, Smith AV, Sofia HJ, Spalding D, Spurdle AB, Stark Z, Stein LD, Suematsu M, Tan P, Tedds JA, Thomson AA, Thorogood A, Tickle TL, Tokunaga K, Törnroos J, Torrents D, Upchurch S, Valencia A, Guimera RV, Vamathevan J, Varma S, Vears DF, Viner C, Voisin C, Wagner AH, Wallace SE, Walsh BP, Williams MS, Winkler EC, Wold BJ, Wood GM, Woolley JP, Yamasaki C, Yates AD, Yung CK, Zass LJ, Zaytseva K, Zhang J, Goodhand P, North K, Birney E.",,Cell genomics,2021,2021-11-01,Y,,,,"The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.",,doi:https://doi.org/10.1016/j.xgen.2021.100029; html:https://europepmc.org/articles/PMC8774288; pdf:https://europepmc.org/articles/PMC8774288?pdf=render diff --git a/data/papers.json b/data/papers.json index 5b9d735f..3777c35f 100644 --- a/data/papers.json +++ b/data/papers.json @@ -1257,23 +1257,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2022.104905" }, - { - "id": "37056776", - "doi": "https://doi.org/10.3389/fimmu.2023.1146702", - "title": "SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.", - "authorString": "Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.", - "authorAffiliations": "", - "journalTitle": "Frontiers in immunology", - "pubYear": "2023", - "date": "2023-03-15", - "isOpenAccess": "Y", - "keywords": "Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically na\u00efve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render" - }, { "id": "34706900", "doi": "https://doi.org/10.1136/emermed-2021-211706", @@ -1325,6 +1308,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2022.101428; html:https://europepmc.org/articles/PMC9096912; pdf:https://europepmc.org/articles/PMC9096912?pdf=render" }, + { + "id": "37056776", + "doi": "https://doi.org/10.3389/fimmu.2023.1146702", + "title": "SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.", + "authorString": "Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.", + "authorAffiliations": "", + "journalTitle": "Frontiers in immunology", + "pubYear": "2023", + "date": "2023-03-15", + "isOpenAccess": "Y", + "keywords": "Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically na\u00efve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render" + }, { "id": "36526323", "doi": "https://doi.org/10.1136/bmjopen-2022-068252", @@ -1563,23 +1563,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/gps.5446; html:https://europepmc.org/articles/PMC7984448; pdf:https://europepmc.org/articles/PMC7984448?pdf=render" }, - { - "id": "34487522", - "doi": "https://doi.org/10.1093/cid/ciab754", - "title": "Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.", - "authorString": "Grint DJ, Wing K, Houlihan C, Gibbs HP, Evans SJW, Williamson E, McDonald HI, Bhaskaran K, Evans D, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AYS, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Smeeth L, Goldacre B, Eggo RM.", - "authorAffiliations": "", - "journalTitle": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", - "pubYear": "2022", - "date": "2022-08-01", - "isOpenAccess": "Y", - "keywords": "Alpha; Hospital Admission; Case Fatality; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death.

Methods

With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021.

Results

Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha\u2005=\u200593 153; wild-type\u2005=\u200592 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P\u2005<\u2005.0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P\u2005<\u2005.0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P\u2005=\u2005.45).

Conclusions

The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/cid/ciab754; html:https://europepmc.org/articles/PMC8522415; pdf:https://europepmc.org/articles/PMC8522415?pdf=render" - }, { "id": "34544601", "doi": "https://doi.org/10.1016/j.vaccine.2021.09.019", @@ -1597,6 +1580,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.vaccine.2021.09.019; html:https://europepmc.org/articles/PMC8423991" }, + { + "id": "34487522", + "doi": "https://doi.org/10.1093/cid/ciab754", + "title": "Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.", + "authorString": "Grint DJ, Wing K, Houlihan C, Gibbs HP, Evans SJW, Williamson E, McDonald HI, Bhaskaran K, Evans D, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AYS, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Smeeth L, Goldacre B, Eggo RM.", + "authorAffiliations": "", + "journalTitle": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", + "pubYear": "2022", + "date": "2022-08-01", + "isOpenAccess": "Y", + "keywords": "Alpha; Hospital Admission; Case Fatality; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death.

Methods

With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021.

Results

Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha\u2005=\u200593 153; wild-type\u2005=\u200592 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P\u2005<\u2005.0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P\u2005<\u2005.0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P\u2005=\u2005.45).

Conclusions

The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/cid/ciab754; html:https://europepmc.org/articles/PMC8522415; pdf:https://europepmc.org/articles/PMC8522415?pdf=render" + }, { "id": "34148733", "doi": "https://doi.org/10.1016/j.bja.2021.05.018", @@ -1971,6 +1971,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ageing/afaa207; html:https://europepmc.org/articles/PMC7546151; pdf:https://europepmc.org/articles/PMC7546151?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/50/1/25/42362959/afaa207.pdf" }, + { + "id": "36807005", + "doi": "https://doi.org/10.1055/a-2038-0541", + "title": "Long-term outcomes of pouch surveillance and risk of neoplasia in familial adenomatous polyposis.", + "authorString": "Patel RV, Curtius K, Man R, Fletcher J, Cuthill V, Clark SK, von Roon AC, Latchford A.", + "authorAffiliations": "", + "journalTitle": "Endoscopy", + "pubYear": "2023", + "date": "2023-02-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

\u2002Long-term pouch surveillance outcomes for familial adenomatous polyposis (FAP) are unknown. We aimed to quantify surveillance outcomes and to determine which of selected possible predictive factors are associated with pouch dysplasia.

Methods

\u2002Retrospective analysis of collected data on 249 patients was performed, analyzing potential risk factors for the development of adenomas or advanced lesions (\u200a\u2265\u200a10\u200amm/high grade dysplasia (HGD)/cancer) in the pouch body and cuff using Cox proportional hazards models. Kaplan-Meier analyses included landmark time-point analyses at 10 years after surgery to predict the future risk of advanced lesions.

Results

\u2002Of 249 patients, 76\u200a% developed at least one pouch body adenoma, with 16\u200a% developing an advanced pouch body lesion; 18\u200a% developed an advanced cuff lesion. Kaplan-Meier analysis showed a 10-year lag before most advanced lesions developed; cumulative incidence of 2.8\u200a% and 6.4\u200a% at 10 years in the pouch body and cuff, respectively. Landmark analysis suggested the presence of adenomas prior to the 10-year point was associated with subsequent development of advanced lesions in the pouch body (hazard ratio [HR] 4.8, 95\u200a%CI 1.6-14.1; P\u200a=\u200a0.004) and cuff (HR 6.8, 95\u200a%CI 2.5-18.3; P\u200a<\u200a0.001). There were two HGD and four cancer cases in the cuff and one pouch body cancer; all cases of cancer/HGD that had prior surveillance were preceded by \u2265\u200a10-mm adenomas.

Conclusions

\u2002Pouch adenoma progression is slow and most advanced lesions occur after 10 years. HGD and cancer were rare events. Pouch phenotype in the first decade is associated with the future risk of developing advanced lesions and may guide personalized surveillance beyond 10 years.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1055/a-2038-0541; html:https://europepmc.org/articles/PMC10465241; pdf:https://europepmc.org/articles/PMC10465241?pdf=render; pdf:http://www.thieme-connect.de/products/ejournals/pdf/10.1055/a-2038-0541.pdf" + }, { "id": "37254630", "doi": "https://doi.org/10.1111/acel.13808", @@ -2209,23 +2226,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph192315544; html:https://europepmc.org/articles/PMC9738189; pdf:https://europepmc.org/articles/PMC9738189?pdf=render" }, - { - "id": "36000189", - "doi": "https://doi.org/10.1515/dx-2022-0052", - "title": "The diagnostic potential and barriers of microbiome based therapeutics.", - "authorString": "Acharjee A, Singh U, Choudhury SP, Gkoutos GV.", - "authorAffiliations": "", - "journalTitle": "Diagnosis (Berlin, Germany)", - "pubYear": "2022", - "date": "2022-08-25", - "isOpenAccess": "N", - "keywords": "Microbiota; Biomarker; Diagnostics; Machine Learning", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "High throughput technological innovations in the past decade have accelerated research into the trillions of commensal microbes in the gut. The 'omics' technologies used for microbiome analysis are constantly evolving, and large-scale datasets are being produced. Despite of the fact that much of the research is still in its early stages, specific microbial signatures have been associated with the\u00a0promotion of cancer, as well as other diseases such as inflammatory bowel disease, neurogenerative diareses etc. It has been also reported that the diversity of the gut microbiome influences the safety and efficacy of medicines. The availability and declining sequencing costs has rendered the employment of RNA-based diagnostics more common in the microbiome field necessitating improved data-analytical techniques so as to fully exploit all the resulting rich biological datasets, while accounting for their unique characteristics, such as their compositional nature as well their heterogeneity and sparsity. As a result, the gut microbiome is increasingly being demonstrating as an important component of personalised medicine since it not only plays a role in inter-individual variability in health and disease, but it also represents a potentially modifiable entity or feature that may be addressed by treatments in a personalised way. In this context, machine learning and artificial intelligence-based methods may be able to unveil new insights into biomedical analyses through the generation of models that may be used to predict category labels, and continuous values. Furthermore, diagnostic aspects will add value in the identification of the non invasive markers in the critical diseases like cancer.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1515/dx-2022-0052" - }, { "id": "35140406", "doi": "https://doi.org/10.1038/s41591-022-01701-w", @@ -2243,6 +2243,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41591-022-01701-w; html:https://europepmc.org/articles/PMC9018414; pdf:https://europepmc.org/articles/PMC9018414?pdf=render" }, + { + "id": "36000189", + "doi": "https://doi.org/10.1515/dx-2022-0052", + "title": "The diagnostic potential and barriers of microbiome based therapeutics.", + "authorString": "Acharjee A, Singh U, Choudhury SP, Gkoutos GV.", + "authorAffiliations": "", + "journalTitle": "Diagnosis (Berlin, Germany)", + "pubYear": "2022", + "date": "2022-08-25", + "isOpenAccess": "N", + "keywords": "Microbiota; Biomarker; Diagnostics; Machine Learning", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "High throughput technological innovations in the past decade have accelerated research into the trillions of commensal microbes in the gut. The 'omics' technologies used for microbiome analysis are constantly evolving, and large-scale datasets are being produced. Despite of the fact that much of the research is still in its early stages, specific microbial signatures have been associated with the\u00a0promotion of cancer, as well as other diseases such as inflammatory bowel disease, neurogenerative diareses etc. It has been also reported that the diversity of the gut microbiome influences the safety and efficacy of medicines. The availability and declining sequencing costs has rendered the employment of RNA-based diagnostics more common in the microbiome field necessitating improved data-analytical techniques so as to fully exploit all the resulting rich biological datasets, while accounting for their unique characteristics, such as their compositional nature as well their heterogeneity and sparsity. As a result, the gut microbiome is increasingly being demonstrating as an important component of personalised medicine since it not only plays a role in inter-individual variability in health and disease, but it also represents a potentially modifiable entity or feature that may be addressed by treatments in a personalised way. In this context, machine learning and artificial intelligence-based methods may be able to unveil new insights into biomedical analyses through the generation of models that may be used to predict category labels, and continuous values. Furthermore, diagnostic aspects will add value in the identification of the non invasive markers in the critical diseases like cancer.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1515/dx-2022-0052" + }, { "id": "36630477", "doi": "https://doi.org/10.1371/journal.pmed.1004156", @@ -2549,23 +2566,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render" }, - { - "id": "37586846", - "doi": "https://doi.org/10.1136/openhrt-2023-002378", - "title": "Cardiovascular imaging research priorities.", - "authorString": "MacArthur JAL, Yong GL, Dweck MR, Fairbairn TA, Weir-McCall J, Puyol-Ant\u00f3n E, Meldrum J, Blakelock P, Khan S, Morrice L, Sudlow CLM, Williams MC.", - "authorAffiliations": "", - "journalTitle": "Open heart", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "Y", - "keywords": "Health Services; Research Design; Diagnostic Imaging", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research.

Methods

First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner.

Results

The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey.

Conclusions

We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/openhrt-2023-002378; html:https://europepmc.org/articles/PMC10432634; pdf:https://europepmc.org/articles/PMC10432634?pdf=render" - }, { "id": "36369151", "doi": "https://doi.org/10.1038/s41467-022-34244-2", @@ -2583,6 +2583,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-022-34244-2; html:https://europepmc.org/articles/PMC9651890; pdf:https://europepmc.org/articles/PMC9651890?pdf=render" }, + { + "id": "37586846", + "doi": "https://doi.org/10.1136/openhrt-2023-002378", + "title": "Cardiovascular imaging research priorities.", + "authorString": "MacArthur JAL, Yong GL, Dweck MR, Fairbairn TA, Weir-McCall J, Puyol-Ant\u00f3n E, Meldrum J, Blakelock P, Khan S, Morrice L, Sudlow CLM, Williams MC.", + "authorAffiliations": "", + "journalTitle": "Open heart", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "Y", + "keywords": "Health Services; Research Design; Diagnostic Imaging", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research.

Methods

First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner.

Results

The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey.

Conclusions

We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/openhrt-2023-002378; html:https://europepmc.org/articles/PMC10432634; pdf:https://europepmc.org/articles/PMC10432634?pdf=render" + }, { "id": "34384736", "doi": "https://doi.org/10.1016/s2589-7500(21)00175-8", @@ -3076,23 +3093,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.06.010; html:https://europepmc.org/articles/PMC9170533; pdf:https://europepmc.org/articles/PMC9170533?pdf=render" }, - { - "id": "37463814", - "doi": "https://doi.org/10.1136/bmjopen-2022-069635", - "title": "HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.", - "authorString": "Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-07-18", - "isOpenAccess": "Y", - "keywords": "Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render" - }, { "id": "34670038", "doi": "https://doi.org/10.1056/nejmc2113864", @@ -3110,6 +3110,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1056/NEJMc2113864; html:https://europepmc.org/articles/PMC8552534; pdf:https://europepmc.org/articles/PMC8552534?pdf=render" }, + { + "id": "37463814", + "doi": "https://doi.org/10.1136/bmjopen-2022-069635", + "title": "HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.", + "authorString": "Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-07-18", + "isOpenAccess": "Y", + "keywords": "Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render" + }, { "id": "37147628", "doi": "https://doi.org/10.1186/s12911-023-02181-9", @@ -3280,23 +3297,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670" }, - { - "id": "37358897", - "doi": "https://doi.org/10.2196/45849", - "title": "Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.", - "authorString": "Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.", - "authorAffiliations": "", - "journalTitle": "JMIR formative research", - "pubYear": "2023", - "date": "2023-06-26", - "isOpenAccess": "Y", - "keywords": "Pain; Mental health; Annotation; Information Extraction; Natural Language Processing", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render; doi:https://doi.org/10.2196/45849" - }, { "id": "36629015", "doi": "https://doi.org/10.1177/17407745221143449", @@ -3314,6 +3314,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/17407745221143449; html:https://europepmc.org/articles/PMC10021127; pdf:https://europepmc.org/articles/PMC10021127?pdf=render" }, + { + "id": "37358897", + "doi": "https://doi.org/10.2196/45849", + "title": "Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.", + "authorString": "Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.", + "authorAffiliations": "", + "journalTitle": "JMIR formative research", + "pubYear": "2023", + "date": "2023-06-26", + "isOpenAccess": "Y", + "keywords": "Pain; Mental health; Annotation; Information Extraction; Natural Language Processing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render; doi:https://doi.org/10.2196/45849" + }, { "id": "35511729", "doi": "https://doi.org/10.1093/ageing/afac084", @@ -3365,23 +3382,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render" }, - { - "id": "36219788", - "doi": "https://doi.org/10.1093/ije/dyac185", - "title": "Borrowing strength from clinical trials in analysing longitudinal data from a treated cohort: investigating the effectiveness of acetylcholinesterase inhibitors in the management of dementia.", - "authorString": "Knight R, Stewart R, Khondoker M, Landau S.", - "authorAffiliations": "", - "journalTitle": "International journal of epidemiology", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "Y", - "keywords": "Cognition; Dementia; Randomized controlled trial; acetylcholinesterase inhibitors; Electronic Medical Record; Bayesian Modelling", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation.

Methods

A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources.

Results

The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12\u2009months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE\u2009=\u20090.316) or cohort data only (1.56, SE\u2009=\u20090.240) overestimated this compared with the estimate using data from both sources (0.86, SE\u2009=\u20090.327).

Conclusions

It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render" - }, { "id": "34104901", "doi": "https://doi.org/10.1016/s2666-7568(21)00093-3", @@ -3416,6 +3416,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738; doi:https://doi.org/10.1016/s1473-3099(21)00289-9" }, + { + "id": "36219788", + "doi": "https://doi.org/10.1093/ije/dyac185", + "title": "Borrowing strength from clinical trials in analysing longitudinal data from a treated cohort: investigating the effectiveness of acetylcholinesterase inhibitors in the management of dementia.", + "authorString": "Knight R, Stewart R, Khondoker M, Landau S.", + "authorAffiliations": "", + "journalTitle": "International journal of epidemiology", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "Y", + "keywords": "Cognition; Dementia; Randomized controlled trial; acetylcholinesterase inhibitors; Electronic Medical Record; Bayesian Modelling", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation.

Methods

A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources.

Results

The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12\u2009months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE\u2009=\u20090.316) or cohort data only (1.56, SE\u2009=\u20090.240) overestimated this compared with the estimate using data from both sources (0.86, SE\u2009=\u20090.327).

Conclusions

It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render" + }, { "id": "35185750", "doi": "https://doi.org/10.3389/fneur.2021.787107", @@ -3705,23 +3722,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/thoraxjnl-2021-218629; html:https://europepmc.org/articles/PMC8983409; pdf:https://europepmc.org/articles/PMC8983409?pdf=render; pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/03/29/thoraxjnl-2021-218629.full.pdf" }, - { - "id": "36526319", - "doi": "https://doi.org/10.1136/bmjopen-2022-064910", - "title": "Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.", - "authorString": "Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-12-16", - "isOpenAccess": "Y", - "keywords": "Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.

Design

Retrospective assessment of routinely collected data from electronic healthcare records.

Setting

Single large urban tertiary care centre.

Participants

All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.

Main outcome measures

Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.

Results

7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.

Conclusions

The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render" - }, { "id": "34446426", "doi": "https://doi.org/10.1136/bmj.n1931", @@ -3739,6 +3739,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmj.n1931; html:https://europepmc.org/articles/PMC8388189; pdf:https://europepmc.org/articles/PMC8388189?pdf=render" }, + { + "id": "36526319", + "doi": "https://doi.org/10.1136/bmjopen-2022-064910", + "title": "Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.", + "authorString": "Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-12-16", + "isOpenAccess": "Y", + "keywords": "Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.

Design

Retrospective assessment of routinely collected data from electronic healthcare records.

Setting

Single large urban tertiary care centre.

Participants

All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.

Main outcome measures

Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.

Results

7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.

Conclusions

The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render" + }, { "id": "31566668", "doi": "https://doi.org/10.1093/ageing/afz110", @@ -3756,23 +3773,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ageing/afz110; html:https://europepmc.org/articles/PMC6814149; pdf:https://europepmc.org/articles/PMC6814149?pdf=render" }, - { - "id": "37181393", - "doi": "https://doi.org/10.1016/j.jacasi.2022.12.006", - "title": "Ambient Temperature and Myocardial\u00a0Infarction: Who Is at Risk?", - "authorString": "Lowry MTH, Mills NL, Kimenai DM.", - "authorAffiliations": "", - "journalTitle": "JACC. Asia", - "pubYear": "2023", - "date": "2023-03-14", - "isOpenAccess": "Y", - "keywords": "Myocardial infarction; Ambient temperature; risk factors", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacasi.2022.12.006; html:https://europepmc.org/articles/PMC10167505; pdf:https://europepmc.org/articles/PMC10167505?pdf=render" - }, { "id": "37387161", "doi": "https://doi.org/10.1093/bioinformatics/btad240", @@ -3790,6 +3790,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/bioinformatics/btad240; html:https://europepmc.org/articles/PMC10311304; pdf:https://europepmc.org/articles/PMC10311304?pdf=render" }, + { + "id": "37181393", + "doi": "https://doi.org/10.1016/j.jacasi.2022.12.006", + "title": "Ambient Temperature and Myocardial\u00a0Infarction: Who Is at Risk?", + "authorString": "Lowry MTH, Mills NL, Kimenai DM.", + "authorAffiliations": "", + "journalTitle": "JACC. Asia", + "pubYear": "2023", + "date": "2023-03-14", + "isOpenAccess": "Y", + "keywords": "Myocardial infarction; Ambient temperature; risk factors", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacasi.2022.12.006; html:https://europepmc.org/articles/PMC10167505; pdf:https://europepmc.org/articles/PMC10167505?pdf=render" + }, { "id": "34304048", "doi": "https://doi.org/10.1016/j.ebiom.2021.103485", @@ -3892,23 +3909,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render" }, - { - "id": "37363796", - "doi": "https://doi.org/10.1016/j.lanepe.2023.100636", - "title": "Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study.", - "authorString": "OpenSAFELY Collaborative, Parker EPK, Horne EMF, Hulme WJ, Tazare J, Zheng B, Carr EJ, Loud F, Lyon S, Mahalingasivam V, MacKenna B, Mehrkar A, Scanlon M, Santhakumaran S, Steenkamp R, Goldacre B, Sterne JAC, Nitsch D, Tomlinson LA, LH&W NCS (or CONVALESCENCE) Collaborative.", - "authorAffiliations": "", - "journalTitle": "The Lancet regional health. Europe", - "pubYear": "2023", - "date": "2023-05-03", - "isOpenAccess": "Y", - "keywords": "Vaccination; Effectiveness; Chronic Kidney Disease; Nhs England; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England.

Methods

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

Findings

After two doses, incidence during the Delta wave was higher in AZ-AZ (n\u00a0=\u00a0257,580) than BNT-BNT recipients (n\u00a0=\u00a0169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n\u00a0=\u00a0220,330) and BNT-BNT-BNT recipients (n\u00a0=\u00a0157,065) for any outcome during a period of Omicron dominance.

Interpretation

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

Funding

National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100636; html:https://europepmc.org/articles/PMC10155829; pdf:https://europepmc.org/articles/PMC10155829?pdf=render" - }, { "id": "32016358", "doi": "https://doi.org/10.1093/ecco-jcc/jjaa021", @@ -3927,21 +3927,21 @@ "urls": "doi:https://doi.org/10.1093/ecco-jcc/jjaa021; html:https://europepmc.org/articles/PMC7392170; pdf:https://europepmc.org/articles/PMC7392170?pdf=render" }, { - "id": "34445233", - "doi": "https://doi.org/10.3390/ijms22168527", - "title": "The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers. ", - "authorString": "Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.", + "id": "37363796", + "doi": "https://doi.org/10.1016/j.lanepe.2023.100636", + "title": "Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study.", + "authorString": "OpenSAFELY Collaborative, Parker EPK, Horne EMF, Hulme WJ, Tazare J, Zheng B, Carr EJ, Loud F, Lyon S, Mahalingasivam V, MacKenna B, Mehrkar A, Scanlon M, Santhakumaran S, Steenkamp R, Goldacre B, Sterne JAC, Nitsch D, Tomlinson LA, LH&W NCS (or CONVALESCENCE) Collaborative.", "authorAffiliations": "", - "journalTitle": "International journal of molecular sciences", - "pubYear": "2021", - "date": "2021-08-08", + "journalTitle": "The Lancet regional health. Europe", + "pubYear": "2023", + "date": "2023-05-03", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Vaccination; Effectiveness; Chronic Kidney Disease; Nhs England; Covid-19; Sars-cov-2", "nationalPriorities": "", "healthCategories": "", - "abstract": "MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.", + "abstract": "

Background

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England.

Methods

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

Findings

After two doses, incidence during the Delta wave was higher in AZ-AZ (n\u00a0=\u00a0257,580) than BNT-BNT recipients (n\u00a0=\u00a0169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n\u00a0=\u00a0220,330) and BNT-BNT-BNT recipients (n\u00a0=\u00a0157,065) for any outcome during a period of Omicron dominance.

Interpretation

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

Funding

National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.", "laySummary": "", - "urls": "doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100636; html:https://europepmc.org/articles/PMC10155829; pdf:https://europepmc.org/articles/PMC10155829?pdf=render" }, { "id": "36941845", @@ -3960,6 +3960,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xkme.2023.100613; html:https://europepmc.org/articles/PMC10024232; pdf:https://europepmc.org/articles/PMC10024232?pdf=render" }, + { + "id": "34445233", + "doi": "https://doi.org/10.3390/ijms22168527", + "title": "The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers. ", + "authorString": "Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.", + "authorAffiliations": "", + "journalTitle": "International journal of molecular sciences", + "pubYear": "2021", + "date": "2021-08-08", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render" + }, { "id": "35473737", "doi": "https://doi.org/10.1136/bmjopen-2021-060413", @@ -4062,23 +4079,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jinf.2023.05.010; html:https://europepmc.org/articles/PMC10176893; pdf:https://europepmc.org/articles/PMC10176893?pdf=render; doi:https://doi.org/10.1016/j.jinf.2023.05.010" }, - { - "id": "37558806", - "doi": "https://doi.org/10.1038/s41598-023-40215-4", - "title": "Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.", - "authorString": "Simonyte S, Grabauskyte I, Macijauskiene J, Lesauskaite V, Lesauskaite V, Kvaal KS, Stewart R.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2023", - "date": "2023-08-09", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65\u00a0years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6\u00a0months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render" - }, { "id": "35226680", "doi": "https://doi.org/10.1371/journal.pone.0264023", @@ -4096,6 +4096,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0264023; html:https://europepmc.org/articles/PMC8884508; pdf:https://europepmc.org/articles/PMC8884508?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264023&type=printable" }, + { + "id": "37558806", + "doi": "https://doi.org/10.1038/s41598-023-40215-4", + "title": "Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.", + "authorString": "Simonyte S, Grabauskyte I, Macijauskiene J, Lesauskaite V, Lesauskaite V, Kvaal KS, Stewart R.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2023", + "date": "2023-08-09", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65\u00a0years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6\u00a0months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render" + }, { "id": "37171130", "doi": "https://doi.org/10.1093/gigascience/giad030", @@ -4130,23 +4147,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/cancers15072031; html:https://europepmc.org/articles/PMC10093616; pdf:https://europepmc.org/articles/PMC10093616?pdf=render" }, - { - "id": "36944118", - "doi": "https://doi.org/10.2337/dc22-1238", - "title": "Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.", - "authorString": "Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.", - "authorAffiliations": "", - "journalTitle": "Diabetes care", - "pubYear": "2023", - "date": "2023-05-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.

Research design and methods

A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.

Results

Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).

Conclusions

Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render" - }, { "id": "32634370", "doi": "https://doi.org/10.1098/rsob.200121", @@ -4164,6 +4164,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1098/rsob.200121; html:https://europepmc.org/articles/PMC7574545; pdf:https://europepmc.org/articles/PMC7574545?pdf=render" }, + { + "id": "36944118", + "doi": "https://doi.org/10.2337/dc22-1238", + "title": "Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.", + "authorString": "Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.", + "authorAffiliations": "", + "journalTitle": "Diabetes care", + "pubYear": "2023", + "date": "2023-05-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.

Research design and methods

A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.

Results

Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).

Conclusions

Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render" + }, { "id": "36530697", "doi": "https://doi.org/10.3389/fpubh.2022.1035415", @@ -4232,23 +4249,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2018-026290; html:https://europepmc.org/articles/PMC6224723; pdf:https://europepmc.org/articles/PMC6224723?pdf=render" }, - { - "id": "36701357", - "doi": "https://doi.org/10.1371/journal.pone.0280943", - "title": "Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.", - "authorString": "Cooper E, Lound A, Atchison CJ, Whitaker M, Eccles C, Cooke GS, Elliott P, Ward H.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-01-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.

Methods

People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.

Results

We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.

Conclusion

This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render" - }, { "id": "34108714", "doi": "https://doi.org/10.1038/s41591-021-01408-4", @@ -4266,6 +4266,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41591-021-01408-4; html:https://europepmc.org/articles/PMC8282499; pdf:https://europepmc.org/articles/PMC8282499?pdf=render; pdf:https://www.nature.com/articles/s41591-021-01408-4.pdf" }, + { + "id": "36701357", + "doi": "https://doi.org/10.1371/journal.pone.0280943", + "title": "Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.", + "authorString": "Cooper E, Lound A, Atchison CJ, Whitaker M, Eccles C, Cooke GS, Elliott P, Ward H.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-01-26", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.

Methods

People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.

Results

We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.

Conclusion

This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render" + }, { "id": "35448463", "doi": "https://doi.org/10.3390/metabo12040276", @@ -4317,23 +4334,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render" }, - { - "id": "37415095", - "doi": "https://doi.org/10.1186/s12889-023-16202-9", - "title": "Multi-morbidity and its association with common cancer diagnoses: a UK Biobank prospective study.", - "authorString": "Conroy MC, Reeves GK, Allen NE.", - "authorAffiliations": "", - "journalTitle": "BMC public health", - "pubYear": "2023", - "date": "2023-07-06", - "isOpenAccess": "Y", - "keywords": "Cancer Risk; Uk Biobank; Multi-morbidity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Whilst multi-morbidity is known to be a concern in people with cancer, very little is known about the risk of cancer in multi-morbid patients. This study aims to investigate the risk of being diagnosed with lung, colorectal, breast and prostate cancer associated with multi-morbidity.

Methods

We investigated the association between multi-morbidity and subsequent risk of cancer diagnosis in UK Biobank. Cox models were used to estimate the relative risks of each cancer of interest in multi-morbid participants, using the Cambridge Multimorbidity Score. The extent to which reverse causation, residual confounding and ascertainment bias may have impacted on the findings was robustly investigated.

Results

Of the 436,990 participants included in the study who were cancer-free at baseline, 21.6% (99,965) were multi-morbid (\u2265\u20092 diseases). Over a median follow-up time of 10.9 [IQR 10.0-11.7] years, 9,019 prostate, 7,994 breast, 5,241 colorectal, and 3,591 lung cancers were diagnosed. After exclusion of the first year of follow-up, there was no clear association between multi-morbidity and risk of colorectal, prostate or breast cancer diagnosis. Those with\u2009\u2265\u20094 diseases at recruitment had double the risk of a subsequent lung cancer diagnosis compared to those with no diseases (HR 2.00 [95% CI 1.70-2.35] p for trend\u2009<\u20090.001). These findings were robust to sensitivity analyses aimed at reducing the impact of reverse causation, residual confounding from known cancer risk factors and ascertainment bias.

Conclusions

Individuals with multi-morbidity are at an increased risk of lung cancer diagnosis. While this association did not appear to be due to common sources of bias in observational studies, further research is needed to understand what underlies this association.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?pdf=render" - }, { "id": "31469943", "doi": "https://doi.org/10.1002/cnm.3255", @@ -4351,6 +4351,23 @@ "laySummary": "This study aimed to measure how well an algorithm using data from non-invasive tests was able to predict early signs of heart disease.", "urls": "doi:https://doi.org/10.1002/cnm.3255; html:https://europepmc.org/articles/PMC7003475; pdf:https://europepmc.org/articles/PMC7003475?pdf=render" }, + { + "id": "37415095", + "doi": "https://doi.org/10.1186/s12889-023-16202-9", + "title": "Multi-morbidity and its association with common cancer diagnoses: a UK Biobank prospective study.", + "authorString": "Conroy MC, Reeves GK, Allen NE.", + "authorAffiliations": "", + "journalTitle": "BMC public health", + "pubYear": "2023", + "date": "2023-07-06", + "isOpenAccess": "Y", + "keywords": "Cancer Risk; Uk Biobank; Multi-morbidity", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Whilst multi-morbidity is known to be a concern in people with cancer, very little is known about the risk of cancer in multi-morbid patients. This study aims to investigate the risk of being diagnosed with lung, colorectal, breast and prostate cancer associated with multi-morbidity.

Methods

We investigated the association between multi-morbidity and subsequent risk of cancer diagnosis in UK Biobank. Cox models were used to estimate the relative risks of each cancer of interest in multi-morbid participants, using the Cambridge Multimorbidity Score. The extent to which reverse causation, residual confounding and ascertainment bias may have impacted on the findings was robustly investigated.

Results

Of the 436,990 participants included in the study who were cancer-free at baseline, 21.6% (99,965) were multi-morbid (\u2265\u20092 diseases). Over a median follow-up time of 10.9 [IQR 10.0-11.7] years, 9,019 prostate, 7,994 breast, 5,241 colorectal, and 3,591 lung cancers were diagnosed. After exclusion of the first year of follow-up, there was no clear association between multi-morbidity and risk of colorectal, prostate or breast cancer diagnosis. Those with\u2009\u2265\u20094 diseases at recruitment had double the risk of a subsequent lung cancer diagnosis compared to those with no diseases (HR 2.00 [95% CI 1.70-2.35] p for trend\u2009<\u20090.001). These findings were robust to sensitivity analyses aimed at reducing the impact of reverse causation, residual confounding from known cancer risk factors and ascertainment bias.

Conclusions

Individuals with multi-morbidity are at an increased risk of lung cancer diagnosis. While this association did not appear to be due to common sources of bias in observational studies, further research is needed to understand what underlies this association.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?pdf=render" + }, { "id": "34440368", "doi": "https://doi.org/10.3390/genes12081194", @@ -4386,38 +4403,38 @@ "urls": "doi:https://doi.org/10.1038/s43856-022-00185-6; html:https://europepmc.org/articles/PMC9546886; pdf:https://europepmc.org/articles/PMC9546886?pdf=render" }, { - "id": "35909058", - "doi": "https://doi.org/10.1016/s2589-7500(22)00123-6", - "title": "Remote COVID-19 Assessment in Primary Care (RECAP) risk prediction tool: derivation and real-world validation studies.", - "authorString": "Espinosa-Gonzalez A, Prociuk D, Fiorentino F, Ramtale C, Mi E, Mi E, Glampson B, Neves AL, Okusi C, Husain L, Macartney J, Brown M, Browne B, Warren C, Chowla R, Heaversedge J, Greenhalgh T, de Lusignan S, Mayer E, Delaney BC.", + "id": "36544046", + "doi": "https://doi.org/10.1038/s41746-022-00730-6", + "title": "A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.", + "authorString": "Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.", "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", + "journalTitle": "NPJ digital medicine", "pubYear": "2022", - "date": "2022-07-28", + "date": "2022-12-21", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO2]) and RECAP-oxygen saturation score (RECAP-O2; with SpO2).

Methods

RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people.

Findings

Data were available from 8311 individuals. Observations, such as SpO2, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO2 was available for 1364 (70\u00b70%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0\u00b780 (95% CI 0\u00b776-0\u00b785) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98\u00b71-99\u00b72; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO2 at rest (as a percentage); the area under the curve was 0\u00b784 (0\u00b778-0\u00b790) and on validation the negative predictive value of low risk designation was 99% (95% CI 98\u00b79-99\u00b77; 1176 of 1183).

Interpretation

Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO2 is available, RECAP-O2 is useful to assess the need for treatment escalation.

Funding

Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.", + "abstract": "Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n\u2009=\u200994; \u00a3\u2009=\u200941.97\u2009m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render" + "urls": "doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render" }, { - "id": "36544046", - "doi": "https://doi.org/10.1038/s41746-022-00730-6", - "title": "A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.", - "authorString": "Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.", + "id": "35909058", + "doi": "https://doi.org/10.1016/s2589-7500(22)00123-6", + "title": "Remote COVID-19 Assessment in Primary Care (RECAP) risk prediction tool: derivation and real-world validation studies.", + "authorString": "Espinosa-Gonzalez A, Prociuk D, Fiorentino F, Ramtale C, Mi E, Mi E, Glampson B, Neves AL, Okusi C, Husain L, Macartney J, Brown M, Browne B, Warren C, Chowla R, Heaversedge J, Greenhalgh T, de Lusignan S, Mayer E, Delaney BC.", "authorAffiliations": "", - "journalTitle": "NPJ digital medicine", + "journalTitle": "The Lancet. Digital health", "pubYear": "2022", - "date": "2022-12-21", + "date": "2022-07-28", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n\u2009=\u200994; \u00a3\u2009=\u200941.97\u2009m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.", + "abstract": "

Background

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO2]) and RECAP-oxygen saturation score (RECAP-O2; with SpO2).

Methods

RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people.

Findings

Data were available from 8311 individuals. Observations, such as SpO2, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO2 was available for 1364 (70\u00b70%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0\u00b780 (95% CI 0\u00b776-0\u00b785) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98\u00b71-99\u00b72; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO2 at rest (as a percentage); the area under the curve was 0\u00b784 (0\u00b778-0\u00b790) and on validation the negative predictive value of low risk designation was 99% (95% CI 98\u00b79-99\u00b77; 1176 of 1183).

Interpretation

Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO2 is available, RECAP-O2 is useful to assess the need for treatment escalation.

Funding

Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render" + "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render" }, { "id": "32851419", @@ -4521,23 +4538,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12916-022-02286-4; html:https://europepmc.org/articles/PMC8860623; pdf:https://europepmc.org/articles/PMC8860623?pdf=render" }, - { - "id": "35492818", - "doi": "https://doi.org/10.1016/j.jaccao.2022.01.102", - "title": "Does Cardiovascular Mortality Overtake\u00a0Cancer Mortality During Cancer\u00a0Survivorship?: An English Retrospective Cohort Study.", - "authorString": "Strongman H, Gadd S, Matthews AA, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.", - "authorAffiliations": "", - "journalTitle": "JACC. CardioOncology", - "pubYear": "2022", - "date": "2022-03-15", - "isOpenAccess": "Y", - "keywords": "Electronic Health Records; Cancer Survivors; Beyond Cancer; Cprd Gold, Clinical Practice Research Datalink Primary Care Data In England", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cancer survivors have a higher risk for developing cardiovascular diseases than the general population.

Objectives

The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death.

Methods

This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults\u00a0\u226540 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation.

Results

Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types\u00a0\u226580 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the\u00a0\u226580-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer.

Conclusions

In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jaccao.2022.01.102; html:https://europepmc.org/articles/PMC9040113; pdf:https://europepmc.org/articles/PMC9040113?pdf=render" - }, { "id": "33745917", "doi": "https://doi.org/10.1016/j.jinf.2021.03.011", @@ -4555,6 +4555,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jinf.2021.03.011; html:https://europepmc.org/articles/PMC7970419; pdf:https://europepmc.org/articles/PMC7970419?pdf=render" }, + { + "id": "35492818", + "doi": "https://doi.org/10.1016/j.jaccao.2022.01.102", + "title": "Does Cardiovascular Mortality Overtake\u00a0Cancer Mortality During Cancer\u00a0Survivorship?: An English Retrospective Cohort Study.", + "authorString": "Strongman H, Gadd S, Matthews AA, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.", + "authorAffiliations": "", + "journalTitle": "JACC. CardioOncology", + "pubYear": "2022", + "date": "2022-03-15", + "isOpenAccess": "Y", + "keywords": "Electronic Health Records; Cancer Survivors; Beyond Cancer; Cprd Gold, Clinical Practice Research Datalink Primary Care Data In England", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cancer survivors have a higher risk for developing cardiovascular diseases than the general population.

Objectives

The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death.

Methods

This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults\u00a0\u226540 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation.

Results

Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types\u00a0\u226580 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the\u00a0\u226580-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer.

Conclusions

In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jaccao.2022.01.102; html:https://europepmc.org/articles/PMC9040113; pdf:https://europepmc.org/articles/PMC9040113?pdf=render" + }, { "id": "35595824", "doi": "https://doi.org/10.1038/s41598-022-12517-6", @@ -4827,23 +4844,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/31021; html:https://europepmc.org/articles/PMC8965669" }, - { - "id": "37434746", - "doi": "https://doi.org/10.1016/j.eclinm.2023.102077", - "title": "Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.", - "authorString": "Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.", - "authorAffiliations": "", - "journalTitle": "EClinicalMedicine", - "pubYear": "2023", - "date": "2023-06-29", - "isOpenAccess": "Y", - "keywords": "Pandemic; Healthcare Utilisation; Ethnic Differences", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods

In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23,\u00a02020.

Findings

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

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render" - }, { "id": "33517931", "doi": "https://doi.org/10.1192/j.eurpsy.2021.6", @@ -4895,23 +4895,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render" }, - { - "id": "37337233", - "doi": "https://doi.org/10.1186/s12916-023-02921-8", - "title": "Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.", - "authorString": "Kimenai DM, Anand A, de Bakker M, Shipley M, Fujisawa T, Lyngbakken MN, Hveem K, Omland T, Valencia-Hern\u00e1ndez CA, Lindbohm JV, Kivimaki M, Singh-Manoux A, Strachan FE, Shah ASV, Kardys I, Boersma E, Brunner EJ, Mills NL.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2023", - "date": "2023-06-19", - "isOpenAccess": "Y", - "keywords": "cardiac troponin; risk factors; Outcome; General Population", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.

Methods

In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements.

Results

In 7,293 individuals (mean 58\u2009\u00b1\u20097\u00a0years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4\u00a0years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction\u2009<\u20090.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75).

Conclusions

Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?pdf=render" - }, { "id": "32565483", "doi": "https://doi.org/10.1136/bmjopen-2020-039097", @@ -4929,6 +4912,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2020-039097; html:https://europepmc.org/articles/PMC7311023; pdf:https://europepmc.org/articles/PMC7311023?pdf=render" }, + { + "id": "37337233", + "doi": "https://doi.org/10.1186/s12916-023-02921-8", + "title": "Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.", + "authorString": "Kimenai DM, Anand A, de Bakker M, Shipley M, Fujisawa T, Lyngbakken MN, Hveem K, Omland T, Valencia-Hern\u00e1ndez CA, Lindbohm JV, Kivimaki M, Singh-Manoux A, Strachan FE, Shah ASV, Kardys I, Boersma E, Brunner EJ, Mills NL.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2023", + "date": "2023-06-19", + "isOpenAccess": "Y", + "keywords": "cardiac troponin; risk factors; Outcome; General Population", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.

Methods

In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements.

Results

In 7,293 individuals (mean 58\u2009\u00b1\u20097\u00a0years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4\u00a0years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction\u2009<\u20090.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75).

Conclusions

Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?pdf=render" + }, { "id": "36987388", "doi": "https://doi.org/10.1177/08862605231163885", @@ -4980,6 +4980,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render" }, + { + "id": "37434746", + "doi": "https://doi.org/10.1016/j.eclinm.2023.102077", + "title": "Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.", + "authorString": "Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.", + "authorAffiliations": "", + "journalTitle": "EClinicalMedicine", + "pubYear": "2023", + "date": "2023-06-29", + "isOpenAccess": "Y", + "keywords": "Pandemic; Healthcare Utilisation; Ethnic Differences", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23,\u00a02020.

Findings

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

Interpretation

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

Funding

LSHTM COVID-19 Response Grant (DONAT15912).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render" + }, { "id": "32405103", "doi": "https://doi.org/10.1016/s0140-6736(20)30854-0", @@ -4997,23 +5014,6 @@ "laySummary": "This paper aims to estimate the excess number of deaths over 1 year associated with covid-19, based on age and underlying conditions. They found that age, sex and underlying conditions do influence background risk, and support the need for sustained stringent suppression measures. They have also developed an online risk calculator prototype which is openly available for anyone to use.", "urls": "doi:https://doi.org/10.1016/S0140-6736(20)30854-0; html:https://europepmc.org/articles/PMC7217641" }, - { - "id": "35192611", - "doi": "https://doi.org/10.1371/journal.pmed.1003916", - "title": "Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.", - "authorString": "McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2022", - "date": "2022-02-22", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods and findings

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

Conclusions

In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render" - }, { "id": "34598993", "doi": "https://doi.org/10.1136/bmjopen-2021-054410", @@ -5031,6 +5031,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render" }, + { + "id": "35192611", + "doi": "https://doi.org/10.1371/journal.pmed.1003916", + "title": "Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.", + "authorString": "McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2022", + "date": "2022-02-22", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods and findings

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

Conclusions

In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render" + }, { "id": "33780469", "doi": "https://doi.org/10.1371/journal.pone.0248195", @@ -5099,23 +5116,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render" }, - { - "id": "35607618", - "doi": "https://doi.org/10.1016/j.patter.2022.100471", - "title": "Relevance, redundancy, and complementarity trade-off (RRCT): A principled, generic, robust feature-selection tool.", - "authorString": "Tsanas A.", - "authorAffiliations": "", - "journalTitle": "Patterns (New York, N.Y.)", - "pubYear": "2022", - "date": "2022-03-31", - "isOpenAccess": "Y", - "keywords": "Information theory; Variable selection; Feature Selection; Statistical Learning; Dimensionality Reduction; Curse Of Dimensionality; Principle Of Parsimony", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "We present a new heuristic feature-selection (FS) algorithm that integrates in a principled algorithmic framework the three key FS components: relevance, redundancy, and complementarity. Thus, we call it relevance, redundancy, and complementarity trade-off (RRCT). The association strength between each feature and the response and between feature pairs is quantified via an information theoretic transformation of rank correlation coefficients, and the feature complementarity is quantified using partial correlation coefficients. We empirically benchmark the performance of RRCT against 19 FS algorithms across four synthetic and eight real-world datasets in indicative challenging settings evaluating the following: (1) matching the true feature set and (2) out-of-sample performance in binary and multi-class classification problems when presenting selected features into a random forest. RRCT is very competitive in both tasks, and we tentatively make suggestions on the generalizability and application of the best-performing FS algorithms across settings where they may operate effectively.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render" - }, { "id": "32990744", "doi": "https://doi.org/10.1093/gigascience/giaa095", @@ -5133,6 +5133,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/gigascience/giaa095; html:https://europepmc.org/articles/PMC7523405; pdf:https://europepmc.org/articles/PMC7523405?pdf=render" }, + { + "id": "35607618", + "doi": "https://doi.org/10.1016/j.patter.2022.100471", + "title": "Relevance, redundancy, and complementarity trade-off (RRCT): A principled, generic, robust feature-selection tool.", + "authorString": "Tsanas A.", + "authorAffiliations": "", + "journalTitle": "Patterns (New York, N.Y.)", + "pubYear": "2022", + "date": "2022-03-31", + "isOpenAccess": "Y", + "keywords": "Information theory; Variable selection; Feature Selection; Statistical Learning; Dimensionality Reduction; Curse Of Dimensionality; Principle Of Parsimony", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "We present a new heuristic feature-selection (FS) algorithm that integrates in a principled algorithmic framework the three key FS components: relevance, redundancy, and complementarity. Thus, we call it relevance, redundancy, and complementarity trade-off (RRCT). The association strength between each feature and the response and between feature pairs is quantified via an information theoretic transformation of rank correlation coefficients, and the feature complementarity is quantified using partial correlation coefficients. We empirically benchmark the performance of RRCT against 19 FS algorithms across four synthetic and eight real-world datasets in indicative challenging settings evaluating the following: (1) matching the true feature set and (2) out-of-sample performance in binary and multi-class classification problems when presenting selected features into a random forest. RRCT is very competitive in both tasks, and we tentatively make suggestions on the generalizability and application of the best-performing FS algorithms across settings where they may operate effectively.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render" + }, { "id": "37068964", "doi": "https://doi.org/10.3399/bjgp.2022.0301", @@ -5218,23 +5235,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ehjqcco/qcaa079; html:https://europepmc.org/articles/PMC7665465; pdf:https://europepmc.org/articles/PMC7665465?pdf=render" }, - { - "id": "33948220", - "doi": "https://doi.org/10.1177/20552076211007661", - "title": "Association between glycosylated haemoglobin and outcomes for patients discharged from hospital with diabetes: A health informatics approach.", - "authorString": "Robbins T, Sankaranarayanan S, Randeva H, Keung SNLC, Arvanitis TN.", - "authorAffiliations": "", - "journalTitle": "Digital health", - "pubYear": "2021", - "date": "2021-01-01", - "isOpenAccess": "Y", - "keywords": "Biochemistry; Diabetes; Hospital Discharge; Readmission; Health Informatics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims/objectives

Extensive research considers associations between inpatient glycaemic control and outcomes during hospital admission; this cautions against overly tight glycaemic targets. Little research considers glycaemic control following hospital discharge. This is despite a clear understanding that people with diabetes are at increased risk of negative outcomes, following discharge. We evaluate absolute and relative Hba1c values, and frequency of Hba1c monitoring, on readmission and mortality rates for people discharged from hospital with diabetes.

Methods

All discharges (n\u2009=\u200946,357) with diabetes from a major tertiary referral centre over 3\u2009years were extracted, including biochemistry data. We conducted an evaluation of association between Hba1c, mortality and readmission, statistical significance and standardised Cohen's D effect size calculations.

Results

399 patients had a Hba1c performed during their admission. 3,138 patients had a Hba1c within 1\u2009year of discharge. Mean average Hba1c for readmissions was 57.82 vs 60.39 for not readmitted (p\u2009=\u20090.009, Cohen's D 0.28). Mean average number of days to Hba1c testing in readmitted was 97 vs 113 for those not readmitted (p\u2009=\u20090.00006, Cohen's D 0.39). Further evaluation of mortality outcomes, cohorts of T1DM and T2DM and association of relative change in Hba1c was performed.

Conclusions

Lower Hba1c values following discharge from hospital are significantly associated with increased risk of readmission, as is a shorter duration until testing. Similar patterns observed for mortality. Findings particularly prominent for T1DM. Further research needed to consider underlying causation and design of appropriate risk stratification models.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render" - }, { "id": "36755846", "doi": "https://doi.org/10.1093/ckj/sfac241", @@ -5253,38 +5253,21 @@ "urls": "doi:https://doi.org/10.1093/ckj/sfac241; html:https://europepmc.org/articles/PMC9900564; pdf:https://europepmc.org/articles/PMC9900564?pdf=render" }, { - "id": "37408471", - "doi": "https://doi.org/10.1093/eurheartj/ehad424", - "title": "The CODE-EHR global framework: lifting the veil on health record data.", - "authorString": "Asselbergs FW, Kotecha D.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-07-06", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/eurheartj/ehad424" - }, - { - "id": "36536453", - "doi": "https://doi.org/10.1186/s41512-022-00137-7", - "title": "Protocol for development and validation of postpartum cardiovascular disease (CVD) risk prediction model incorporating reproductive and pregnancy-related candidate predictors.", - "authorString": "Wambua S, Crowe F, Thangaratinam S, O'Reilly D, McCowan C, Brophy S, Yau C, Nirantharakumar K, Riley R, MuM-PreDiCT Group.", + "id": "33948220", + "doi": "https://doi.org/10.1177/20552076211007661", + "title": "Association between glycosylated haemoglobin and outcomes for patients discharged from hospital with diabetes: A health informatics approach.", + "authorString": "Robbins T, Sankaranarayanan S, Randeva H, Keung SNLC, Arvanitis TN.", "authorAffiliations": "", - "journalTitle": "Diagnostic and prognostic research", - "pubYear": "2022", - "date": "2022-12-19", + "journalTitle": "Digital health", + "pubYear": "2021", + "date": "2021-01-01", "isOpenAccess": "Y", - "keywords": "Prognosis; Cardiovascular disease; Pregnant women; Pregnancy complications; Prediction Modeling", + "keywords": "Biochemistry; Diabetes; Hospital Discharge; Readmission; Health Informatics", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Cardiovascular disease (CVD) is a leading cause of death among women. CVD is associated with reduced quality of life, significant treatment and management costs, and lost productivity. Estimating the risk of CVD would help patients at a higher risk of CVD to initiate preventive measures to reduce risk of disease. The Framingham risk score and the QRISK\u00ae score are two risk prediction models used to evaluate future CVD risk in the UK. Although the algorithms perform well in the general population, they do not take into account pregnancy complications, which are well known risk factors for CVD in women and have been highlighted in a recent umbrella review. We plan to develop a robust CVD risk prediction model to assess the additional value of pregnancy risk factors in risk prediction of CVD in women postpartum.

Methods

Using candidate predictors from QRISK\u00ae-3, the umbrella review identified from literature and from discussions with clinical experts and patient research partners, we will use time-to-event Cox proportional hazards models to develop and validate a 10-year risk prediction model for CVD postpartum using Clinical Practice Research Datalink (CPRD) primary care database for development and internal validation of the algorithm and the Secure Anonymised Information Linkage (SAIL) databank for external validation. We will then assess the value of additional candidate predictors to the QRISK\u00ae-3 in our internal and external validations.

Discussion

The developed risk prediction model will incorporate pregnancy-related factors which have been shown to be associated with future risk of CVD but have not been taken into account in current risk prediction models. Our study will therefore highlight the importance of incorporating pregnancy-related risk factors into risk prediction modeling for CVD postpartum.", + "abstract": "

Aims/objectives

Extensive research considers associations between inpatient glycaemic control and outcomes during hospital admission; this cautions against overly tight glycaemic targets. Little research considers glycaemic control following hospital discharge. This is despite a clear understanding that people with diabetes are at increased risk of negative outcomes, following discharge. We evaluate absolute and relative Hba1c values, and frequency of Hba1c monitoring, on readmission and mortality rates for people discharged from hospital with diabetes.

Methods

All discharges (n\u2009=\u200946,357) with diabetes from a major tertiary referral centre over 3\u2009years were extracted, including biochemistry data. We conducted an evaluation of association between Hba1c, mortality and readmission, statistical significance and standardised Cohen's D effect size calculations.

Results

399 patients had a Hba1c performed during their admission. 3,138 patients had a Hba1c within 1\u2009year of discharge. Mean average Hba1c for readmissions was 57.82 vs 60.39 for not readmitted (p\u2009=\u20090.009, Cohen's D 0.28). Mean average number of days to Hba1c testing in readmitted was 97 vs 113 for those not readmitted (p\u2009=\u20090.00006, Cohen's D 0.39). Further evaluation of mortality outcomes, cohorts of T1DM and T2DM and association of relative change in Hba1c was performed.

Conclusions

Lower Hba1c values following discharge from hospital are significantly associated with increased risk of readmission, as is a shorter duration until testing. Similar patterns observed for mortality. Findings particularly prominent for T1DM. Further research needed to consider underlying causation and design of appropriate risk stratification models.", "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s41512-022-00137-7; html:https://europepmc.org/articles/PMC9761974; pdf:https://europepmc.org/articles/PMC9761974?pdf=render" + "urls": "doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render" }, { "id": "34474011", @@ -5303,6 +5286,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S0140-6736(21)01638-X; html:https://europepmc.org/articles/PMC8542730; doi:https://doi.org/10.1016/s0140-6736(21)01638-x" }, + { + "id": "37408471", + "doi": "https://doi.org/10.1093/eurheartj/ehad424", + "title": "The CODE-EHR global framework: lifting the veil on health record data.", + "authorString": "Asselbergs FW, Kotecha D.", + "authorAffiliations": "", + "journalTitle": "European heart journal", + "pubYear": "2023", + "date": "2023-07-06", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/eurheartj/ehad424" + }, { "id": "34432797", "doi": "https://doi.org/10.1371/journal.pone.0255748", @@ -5320,6 +5320,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0255748; html:https://europepmc.org/articles/PMC8386866; pdf:https://europepmc.org/articles/PMC8386866?pdf=render" }, + { + "id": "36536453", + "doi": "https://doi.org/10.1186/s41512-022-00137-7", + "title": "Protocol for development and validation of postpartum cardiovascular disease (CVD) risk prediction model incorporating reproductive and pregnancy-related candidate predictors.", + "authorString": "Wambua S, Crowe F, Thangaratinam S, O'Reilly D, McCowan C, Brophy S, Yau C, Nirantharakumar K, Riley R, MuM-PreDiCT Group.", + "authorAffiliations": "", + "journalTitle": "Diagnostic and prognostic research", + "pubYear": "2022", + "date": "2022-12-19", + "isOpenAccess": "Y", + "keywords": "Prognosis; Cardiovascular disease; Pregnant women; Pregnancy complications; Prediction Modeling", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cardiovascular disease (CVD) is a leading cause of death among women. CVD is associated with reduced quality of life, significant treatment and management costs, and lost productivity. Estimating the risk of CVD would help patients at a higher risk of CVD to initiate preventive measures to reduce risk of disease. The Framingham risk score and the QRISK\u00ae score are two risk prediction models used to evaluate future CVD risk in the UK. Although the algorithms perform well in the general population, they do not take into account pregnancy complications, which are well known risk factors for CVD in women and have been highlighted in a recent umbrella review. We plan to develop a robust CVD risk prediction model to assess the additional value of pregnancy risk factors in risk prediction of CVD in women postpartum.

Methods

Using candidate predictors from QRISK\u00ae-3, the umbrella review identified from literature and from discussions with clinical experts and patient research partners, we will use time-to-event Cox proportional hazards models to develop and validate a 10-year risk prediction model for CVD postpartum using Clinical Practice Research Datalink (CPRD) primary care database for development and internal validation of the algorithm and the Secure Anonymised Information Linkage (SAIL) databank for external validation. We will then assess the value of additional candidate predictors to the QRISK\u00ae-3 in our internal and external validations.

Discussion

The developed risk prediction model will incorporate pregnancy-related factors which have been shown to be associated with future risk of CVD but have not been taken into account in current risk prediction models. Our study will therefore highlight the importance of incorporating pregnancy-related risk factors into risk prediction modeling for CVD postpartum.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s41512-022-00137-7; html:https://europepmc.org/articles/PMC9761974; pdf:https://europepmc.org/articles/PMC9761974?pdf=render" + }, { "id": "34238721", "doi": "https://doi.org/10.1016/s2589-7500(21)00105-9", @@ -5624,7 +5641,7 @@ "healthCategories": "", "abstract": "

Objectives

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

Design

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

Setting

Children attending primary schools in Wales (2018-2020), UK, who were part of the Health and Attainment of Pupils in a Primary Education Network (HAPPEN)_school network.

Participants

Complete linked records of eligible participants were obtained for n=7062 individuals. 39.1% (n=2764) were tested (age 10.6\u00b10.9; 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6\u00b11.0; 54.5% girls).

Main outcome measures

Logistic regression of health-related behaviours and demographics were used to determine the ORs of factors associated with (1) being tested for SARS-CoV-2 and (2) testing positive for SARS-CoV-2.

Results

Consuming sugary snacks (1-2\u2009days/week OR=1.24, 95% CI 1.04 to 1.49; 5-6\u2009days/week OR=1.31, 95% CI 1.07 to 1.61; reference 0 days), can swim 25 m (OR=1.21, 95% CI 1.06 to 1.39) and age (OR=1.25, 95% CI 1.16 to 1.35) were associated with an increased likelihood of being tested for SARS-CoV-2. Eating breakfast (OR=1.52, 95% CI 1.01 to 2.27), weekly physical activity \u226560 min (1-2\u2009days OR=1.69, 95% CI 1.04 to 2.74; 3-4\u2009days OR=1.76, 95% CI 1.10 to 2.82; reference 0 days), out-of-school club participation (OR=1.06, 95% CI 1.02 to 1.10), can ride a bike (OR=1.39, 95% CI 1.00 to 1.93), age (OR=1.16, 95% CI 1.05 to 1.28) and girls (OR=1.21, 95% CI 1.00 to 1.46) were associated with an increased likelihood of testing positive for SARS-CoV-2. Living in least deprived areas (quintile 4 OR=0.64, 95% CI 0.46 to 0.90; quintile 5 OR=0.64, 95% CI 0.46 to 0.89) compared with the most deprived (quintile 1) was associated with a decreased likelihood.

Conclusions

Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include coparticipation with others and exposure to SARS-CoV-2. A risk-versus-benefit approach must be considered in relation to promoting these health behaviours, given the importance of health-related behaviours such as childhood physical activity for development.", "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?pdf=render" + "urls": "doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e061344.full.pdf" }, { "id": "35922409", @@ -5677,23 +5694,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.23889/ijpds.v7i1.1717; html:https://europepmc.org/articles/PMC9284510; pdf:https://europepmc.org/articles/PMC9284510?pdf=render; pdf:https://ijpds.org/article/download/1717/3510" }, - { - "id": "36863848", - "doi": "https://doi.org/10.1136/archdischild-2022-325152", - "title": "Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.", - "authorString": "Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.", - "authorAffiliations": "", - "journalTitle": "Archives of disease in childhood", - "pubYear": "2023", - "date": "2023-03-02", - "isOpenAccess": "Y", - "keywords": "epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.

Design

Serial cross-sectional study.

Setting

Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).

Study population

Children aged 5-17 years in the community.

Predictors

Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.

Main outcome measures

Prevalence of persistent symptoms, reported as those lasting \u22653 months post-COVID-19.

Results

Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11\u2009year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17\u2009year-olds with prior symptomatic infection reported at least one symptom lasting \u22653 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.

Conclusions

One in 23 5-11\u2009year-olds and one in eight 12-17\u2009year-olds post-COVID-19 report persistent symptoms lasting \u22653 months, of which one in nine report a large impact on performing day-to-day activities.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render" - }, { "id": "34461893", "doi": "https://doi.org/10.1186/s12916-021-02096-0", @@ -5711,6 +5711,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render" }, + { + "id": "36863848", + "doi": "https://doi.org/10.1136/archdischild-2022-325152", + "title": "Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.", + "authorString": "Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.", + "authorAffiliations": "", + "journalTitle": "Archives of disease in childhood", + "pubYear": "2023", + "date": "2023-03-02", + "isOpenAccess": "Y", + "keywords": "epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.

Design

Serial cross-sectional study.

Setting

Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).

Study population

Children aged 5-17 years in the community.

Predictors

Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.

Main outcome measures

Prevalence of persistent symptoms, reported as those lasting \u22653 months post-COVID-19.

Results

Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11\u2009year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17\u2009year-olds with prior symptomatic infection reported at least one symptom lasting \u22653 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.

Conclusions

One in 23 5-11\u2009year-olds and one in eight 12-17\u2009year-olds post-COVID-19 report persistent symptoms lasting \u22653 months, of which one in nine report a large impact on performing day-to-day activities.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render" + }, { "id": "PMC10464864", "doi": "https://doi.org/", @@ -5966,23 +5983,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1192/bjo.2022.24; html:https://europepmc.org/articles/PMC8935938; pdf:https://europepmc.org/articles/PMC8935938?pdf=render" }, - { - "id": "33240522", - "doi": "https://doi.org/10.1177/2055207620965046", - "title": "Electronic-prescribing tools improve N-acetylcysteine prescription accuracy and timeliness for patients who present following a paracetamol overdose: A digital innovation quality-improvement project.", - "authorString": "McCulloch A, Sarwar A, Bate T, Thompson D, McDowell P, Sharif Q, Sapey E, Seccombe A.", - "authorAffiliations": "", - "journalTitle": "Digital health", - "pubYear": "2020", - "date": "2020-01-01", - "isOpenAccess": "Y", - "keywords": "Antidote; Digital; paracetamol; Prescription Errors; Electronic Health Systems", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Prescription error rates and delays in treatment provision are high for N-acetylcysteine (NAC) when prescribed for paracetamol overdose (POD). We hypothesised that an electronic tool which proposed the complete NAC regimen would reduce prescription errors and improve the timeliness of NAC provision. Error rates and delays in the provision of NAC were assessed following POD, before and after the implementation of an electronic prescribing tool.

Methods

The NAC electronic prescribing tool proposed the three NAC infusions (dosed for weight) following entry of the patient's weight. All NAC prescriptions were reviewed during a three-month period prior to and after the tool's implementation. Error rates were divided into dose, infusion volume or infusion rate. Delays in NAC provision were identified using national Emergency Medicine guidelines.

Results

108 NAC prescriptions were analysed for all adult patients admitted to the emergency department of a secondary care hospital in the UK between July-September 2017 and August-October 2018, respectively. There were no differences in the demographics of patients or the seniority of the prescribing clinician before or after the introduction of the electronic tool. The electronic prescribing tool was associated with a decrease in prescribing errors (25% to 0%, p\u2009<\u20090.0071) and an increase in the provision of NAC within recommended times (11.1% to 47.4%, p\u2009=\u20090.029).

Conclusions

An electronic prescribing tool improved prescription errors and the timeliness of NAC provision following POD. Further studies will determine the effect of this on length of stay and the benefit of wider implementation in other secondary care hospitals.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render" - }, { "id": "34376451", "doi": "https://doi.org/10.1136/bmjopen-2021-048852", @@ -6000,6 +6000,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-048852; html:https://europepmc.org/articles/PMC8359861; pdf:https://europepmc.org/articles/PMC8359861?pdf=render" }, + { + "id": "33240522", + "doi": "https://doi.org/10.1177/2055207620965046", + "title": "Electronic-prescribing tools improve N-acetylcysteine prescription accuracy and timeliness for patients who present following a paracetamol overdose: A digital innovation quality-improvement project.", + "authorString": "McCulloch A, Sarwar A, Bate T, Thompson D, McDowell P, Sharif Q, Sapey E, Seccombe A.", + "authorAffiliations": "", + "journalTitle": "Digital health", + "pubYear": "2020", + "date": "2020-01-01", + "isOpenAccess": "Y", + "keywords": "Antidote; Digital; paracetamol; Prescription Errors; Electronic Health Systems", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Prescription error rates and delays in treatment provision are high for N-acetylcysteine (NAC) when prescribed for paracetamol overdose (POD). We hypothesised that an electronic tool which proposed the complete NAC regimen would reduce prescription errors and improve the timeliness of NAC provision. Error rates and delays in the provision of NAC were assessed following POD, before and after the implementation of an electronic prescribing tool.

Methods

The NAC electronic prescribing tool proposed the three NAC infusions (dosed for weight) following entry of the patient's weight. All NAC prescriptions were reviewed during a three-month period prior to and after the tool's implementation. Error rates were divided into dose, infusion volume or infusion rate. Delays in NAC provision were identified using national Emergency Medicine guidelines.

Results

108 NAC prescriptions were analysed for all adult patients admitted to the emergency department of a secondary care hospital in the UK between July-September 2017 and August-October 2018, respectively. There were no differences in the demographics of patients or the seniority of the prescribing clinician before or after the introduction of the electronic tool. The electronic prescribing tool was associated with a decrease in prescribing errors (25% to 0%, p\u2009<\u20090.0071) and an increase in the provision of NAC within recommended times (11.1% to 47.4%, p\u2009=\u20090.029).

Conclusions

An electronic prescribing tool improved prescription errors and the timeliness of NAC provision following POD. Further studies will determine the effect of this on length of stay and the benefit of wider implementation in other secondary care hospitals.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render" + }, { "id": "35902613", "doi": "https://doi.org/10.1038/s41467-022-32096-4", @@ -6272,23 +6289,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1080/09553002.2023.2173823" }, - { - "id": "36447940", - "doi": "https://doi.org/10.1016/s2665-9913(22)00305-8", - "title": "Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.", - "authorString": "Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Rheumatology", - "pubYear": "2022", - "date": "2022-11-03", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17\u00b77 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17\u2008683\u2008500 adults, there were 31\u2008280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55\u00b74 years (SD 16\u00b76), 18\u2008615 (59\u00b75%) were female, 12\u2008665 (40\u00b75%) were male, and 22\u2008925 (88\u00b73%) of 25\u2008960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20\u00b73% in the year commencing April, 2020, relative to the preceding year (5\u00b71 vs 6\u00b74 diagnoses per 10\u2008000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render" - }, { "id": "33243817", "doi": "https://doi.org/10.1136/bmjopen-2020-042813", @@ -6323,6 +6323,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12933-022-01482-z; html:https://europepmc.org/articles/PMC8981770; pdf:https://europepmc.org/articles/PMC8981770?pdf=render" }, + { + "id": "36447940", + "doi": "https://doi.org/10.1016/s2665-9913(22)00305-8", + "title": "Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.", + "authorString": "Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Rheumatology", + "pubYear": "2022", + "date": "2022-11-03", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17\u00b77 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17\u2008683\u2008500 adults, there were 31\u2008280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55\u00b74 years (SD 16\u00b76), 18\u2008615 (59\u00b75%) were female, 12\u2008665 (40\u00b75%) were male, and 22\u2008925 (88\u00b73%) of 25\u2008960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20\u00b73% in the year commencing April, 2020, relative to the preceding year (5\u00b71 vs 6\u00b74 diagnoses per 10\u2008000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render" + }, { "id": "32935048", "doi": "https://doi.org/10.23889/ijpds.v5i1.1121", @@ -6357,23 +6374,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-020-73228-4; html:https://europepmc.org/articles/PMC7529768; pdf:https://europepmc.org/articles/PMC7529768?pdf=render" }, - { - "id": "37236697", - "doi": "https://doi.org/10.1016/s2589-7500(23)00065-1", - "title": "Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study.", - "authorString": "Banerjee A, Dashtban A, Chen S, Pasea L, Thygesen JH, Fatemifar G, Tyl B, Dyszynski T, Asselbergs FW, Lund LH, Lumbers T, Denaxas S, Hemingway H.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Machine learning has been used to analyse heart failure subtypes, but not across large, distinct, population-based datasets, across the whole spectrum of causes and presentations, or with clinical and non-clinical validation by different machine learning methods. Using our published framework, we aimed to discover heart failure subtypes and validate them upon population representative data.

Methods

In this external, prognostic, and genetic validation study we analysed individuals aged 30 years or older with incident heart failure from two population-based databases in the UK (Clinical Practice Research Datalink [CPRD] and The Health Improvement Network [THIN]) from 1998 to 2018. Pre-heart failure and post-heart failure factors (n=645) included demographic information, history, examination, blood laboratory values, and medications. We identified subtypes using four unsupervised machine learning methods (K-means, hierarchical, K-Medoids, and mixture model clustering) with 87 of 645 factors in each dataset. We evaluated subtypes for (1) external validity (across datasets); (2) prognostic validity (predictive accuracy for 1-year mortality); and (3) genetic validity (UK Biobank), association with polygenic risk score (PRS) for heart failure-related traits (n=11), and single nucleotide polymorphisms (n=12).

Findings

We included 188\u2008800, 124\u2008262, and 9573 individuals with incident heart failure from CPRD, THIN, and UK Biobank, respectively, between Jan 1, 1998, and Jan 1, 2018. After identifying five clusters, we labelled heart failure subtypes as (1) early onset, (2) late onset, (3) atrial fibrillation related, (4) metabolic, and (5) cardiometabolic. In the external validity analysis, subtypes were similar across datasets (c-statistics: THIN model in CPRD ranged from 0\u00b779 [subtype 3] to 0\u00b794 [subtype 1], and CPRD model in THIN ranged from 0\u00b779 [subtype 1] to 0\u00b792 [subtypes 2 and 5]). In the prognostic validity analysis, 1-year all-cause mortality after heart failure diagnosis (subtype 1 0\u00b720 [95% CI 0\u00b714-0\u00b725], subtype 2 0\u00b746 [0\u00b743-0\u00b749], subtype 3 0\u00b761 [0\u00b757-0\u00b764], subtype 4 0\u00b711 [0\u00b707-0\u00b716], and subtype 5 0\u00b737 [0\u00b732-0\u00b741]) differed across subtypes in CPRD and THIN data, as did risk of non-fatal cardiovascular diseases and all-cause hospitalisation. In the genetic validity analysis the atrial fibrillation-related subtype showed associations with the related PRS. Late onset and cardiometabolic subtypes were the most similar and strongly associated with PRS for hypertension, myocardial infarction, and obesity (p<0\u00b70009). We developed a prototype app for routine clinical use, which could enable evaluation of effectiveness and cost-effectiveness.

Interpretation

Across four methods and three datasets, including genetic data, in the largest study of incident heart failure to date, we identified five machine learning-informed subtypes, which might inform aetiological research, clinical risk prediction, and the design of heart failure trials.

Funding

European Union Innovative Medicines Initiative-2.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2589-7500(23)00065-1" - }, { "id": "33611594", "doi": "https://doi.org/10.1093/eurjpc/zwaa155", @@ -6391,6 +6391,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/eurjpc/zwaa155; html:https://europepmc.org/articles/PMC7928969; pdf:https://europepmc.org/articles/PMC7928969?pdf=render; pdf:https://academic.oup.com/eurjpc/article-pdf/28/14/1599/41827245/zwaa155.pdf" }, + { + "id": "37236697", + "doi": "https://doi.org/10.1016/s2589-7500(23)00065-1", + "title": "Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study.", + "authorString": "Banerjee A, Dashtban A, Chen S, Pasea L, Thygesen JH, Fatemifar G, Tyl B, Dyszynski T, Asselbergs FW, Lund LH, Lumbers T, Denaxas S, Hemingway H.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Machine learning has been used to analyse heart failure subtypes, but not across large, distinct, population-based datasets, across the whole spectrum of causes and presentations, or with clinical and non-clinical validation by different machine learning methods. Using our published framework, we aimed to discover heart failure subtypes and validate them upon population representative data.

Methods

In this external, prognostic, and genetic validation study we analysed individuals aged 30 years or older with incident heart failure from two population-based databases in the UK (Clinical Practice Research Datalink [CPRD] and The Health Improvement Network [THIN]) from 1998 to 2018. Pre-heart failure and post-heart failure factors (n=645) included demographic information, history, examination, blood laboratory values, and medications. We identified subtypes using four unsupervised machine learning methods (K-means, hierarchical, K-Medoids, and mixture model clustering) with 87 of 645 factors in each dataset. We evaluated subtypes for (1) external validity (across datasets); (2) prognostic validity (predictive accuracy for 1-year mortality); and (3) genetic validity (UK Biobank), association with polygenic risk score (PRS) for heart failure-related traits (n=11), and single nucleotide polymorphisms (n=12).

Findings

We included 188\u2008800, 124\u2008262, and 9573 individuals with incident heart failure from CPRD, THIN, and UK Biobank, respectively, between Jan 1, 1998, and Jan 1, 2018. After identifying five clusters, we labelled heart failure subtypes as (1) early onset, (2) late onset, (3) atrial fibrillation related, (4) metabolic, and (5) cardiometabolic. In the external validity analysis, subtypes were similar across datasets (c-statistics: THIN model in CPRD ranged from 0\u00b779 [subtype 3] to 0\u00b794 [subtype 1], and CPRD model in THIN ranged from 0\u00b779 [subtype 1] to 0\u00b792 [subtypes 2 and 5]). In the prognostic validity analysis, 1-year all-cause mortality after heart failure diagnosis (subtype 1 0\u00b720 [95% CI 0\u00b714-0\u00b725], subtype 2 0\u00b746 [0\u00b743-0\u00b749], subtype 3 0\u00b761 [0\u00b757-0\u00b764], subtype 4 0\u00b711 [0\u00b707-0\u00b716], and subtype 5 0\u00b737 [0\u00b732-0\u00b741]) differed across subtypes in CPRD and THIN data, as did risk of non-fatal cardiovascular diseases and all-cause hospitalisation. In the genetic validity analysis the atrial fibrillation-related subtype showed associations with the related PRS. Late onset and cardiometabolic subtypes were the most similar and strongly associated with PRS for hypertension, myocardial infarction, and obesity (p<0\u00b70009). We developed a prototype app for routine clinical use, which could enable evaluation of effectiveness and cost-effectiveness.

Interpretation

Across four methods and three datasets, including genetic data, in the largest study of incident heart failure to date, we identified five machine learning-informed subtypes, which might inform aetiological research, clinical risk prediction, and the design of heart failure trials.

Funding

European Union Innovative Medicines Initiative-2.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2589-7500(23)00065-1" + }, { "id": "34599527", "doi": "https://doi.org/10.1111/dme.14707", @@ -6680,6 +6697,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render" }, + { + "id": "35474585", + "doi": "https://doi.org/10.1111/bcp.15366", + "title": "Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.", + "authorString": "Subramanian A, Han D, Braithwaite T, Thayakaran R, Zemedikun DT, Gokhale KM, Lee WH, Coker J, Keane PA, Denniston AK, Nirantharakumar K, Azoulay L, Adderley NJ.", + "authorAffiliations": "", + "journalTitle": "British journal of clinical pharmacology", + "pubYear": "2022", + "date": "2022-05-11", + "isOpenAccess": "Y", + "keywords": "Hypertension; Angiotensin-converting enzyme inhibitors; Age-related macular degeneration", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40\u2009years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.

Methods

In this study, 53\u2009832 and 43\u2009106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.

Results

During a median follow-up of 2\u00a0years (interquartile range 1-5\u00a0years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively).

Conclusion

We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/bcp.15366; html:https://europepmc.org/articles/PMC9541840; pdf:https://europepmc.org/articles/PMC9541840?pdf=render" + }, { "id": "34782484", "doi": "https://doi.org/10.1136/thoraxjnl-2021-217580", @@ -6714,23 +6748,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/jech-2020-214051; html:https://europepmc.org/articles/PMC7307459; pdf:https://europepmc.org/articles/PMC7307459?pdf=render; pdf:https://jech.bmj.com/content/jech/74/10/861.full.pdf" }, - { - "id": "35474585", - "doi": "https://doi.org/10.1111/bcp.15366", - "title": "Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.", - "authorString": "Subramanian A, Han D, Braithwaite T, Thayakaran R, Zemedikun DT, Gokhale KM, Lee WH, Coker J, Keane PA, Denniston AK, Nirantharakumar K, Azoulay L, Adderley NJ.", - "authorAffiliations": "", - "journalTitle": "British journal of clinical pharmacology", - "pubYear": "2022", - "date": "2022-05-11", - "isOpenAccess": "Y", - "keywords": "Hypertension; Angiotensin-converting enzyme inhibitors; Age-related macular degeneration", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40\u2009years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.

Methods

In this study, 53\u2009832 and 43\u2009106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.

Results

During a median follow-up of 2\u00a0years (interquartile range 1-5\u00a0years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively).

Conclusion

We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1111/bcp.15366; html:https://europepmc.org/articles/PMC9541840; pdf:https://europepmc.org/articles/PMC9541840?pdf=render" - }, { "id": "33114263", "doi": "https://doi.org/10.3390/ijms21217886", @@ -7020,23 +7037,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644982; pdf:https://europepmc.org/articles/PMC9644982?pdf=render" }, - { - "id": "34644365", - "doi": "https://doi.org/10.1371/journal.pone.0258484", - "title": "Cohort profile: The UK COVID-19 Public Experiences (COPE) prospective longitudinal mixed-methods study of health and well-being during the SARSCoV2 coronavirus pandemic.", - "authorString": "Phillips R, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Peddle S, Campbell S, Hughes K, Gillespie D, Sellars P, Pell B, Ashfield-Watt P, Akbari A, Seage CH, Perham N, Joseph-Williams N, Harrop E, Blaxland J, Wood F, Poortinga W, Wahl-Jorgensen K, James DH, Crone D, Thomas-Jones E, Hallingberg B.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2021", - "date": "2021-10-13", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook\u00ae, Twitter\u00ae, Instagram\u00ae). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0258484; html:https://europepmc.org/articles/PMC8513913; pdf:https://europepmc.org/articles/PMC8513913?pdf=render" - }, { "id": "34632260", "doi": "https://doi.org/10.1093/rap/rkab042", @@ -7054,6 +7054,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/rap/rkab042; html:https://europepmc.org/articles/PMC8496109; pdf:https://europepmc.org/articles/PMC8496109?pdf=render" }, + { + "id": "34644365", + "doi": "https://doi.org/10.1371/journal.pone.0258484", + "title": "Cohort profile: The UK COVID-19 Public Experiences (COPE) prospective longitudinal mixed-methods study of health and well-being during the SARSCoV2 coronavirus pandemic.", + "authorString": "Phillips R, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Peddle S, Campbell S, Hughes K, Gillespie D, Sellars P, Pell B, Ashfield-Watt P, Akbari A, Seage CH, Perham N, Joseph-Williams N, Harrop E, Blaxland J, Wood F, Poortinga W, Wahl-Jorgensen K, James DH, Crone D, Thomas-Jones E, Hallingberg B.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2021", + "date": "2021-10-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook\u00ae, Twitter\u00ae, Instagram\u00ae). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pone.0258484; html:https://europepmc.org/articles/PMC8513913; pdf:https://europepmc.org/articles/PMC8513913?pdf=render" + }, { "id": "36992264", "doi": "https://doi.org/10.3390/vaccines11030680", @@ -7122,23 +7139,6 @@ "laySummary": "", "urls": "html:https://europepmc.org/articles/PMC8581917; pdf:https://europepmc.org/articles/PMC8581917?pdf=render" }, - { - "id": "35997000", - "doi": "https://doi.org/10.1111/ene.15530", - "title": "Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.", - "authorString": "Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.", - "authorAffiliations": "", - "journalTitle": "European journal of neurology", - "pubYear": "2022", - "date": "2022-09-11", - "isOpenAccess": "Y", - "keywords": "Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background and purpose

Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.

Methods

A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.

Results

Individuals with idiopathic dystonia (n\u00a0=\u200952,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n\u00a0=\u2009216,754, 43% vs. 31%, p\u00a0<\u20090.001; 45% vs. 37.9%, p\u00a0<\u20090.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR]\u2009=\u20091.98, 95% confidence interval [CI]\u2009=\u20091.9-2.1), with an IRR of 12.4 (95% CI\u00a0=\u00a011.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR\u00a0=\u00a01.96, 95% CI\u00a0=\u00a01.85-2.07).

Conclusions

This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render" - }, { "id": "35003715", "doi": "https://doi.org/10.7189/jogh.11.05026", @@ -7156,6 +7156,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7189/jogh.11.05026; html:https://europepmc.org/articles/PMC8709900; pdf:https://europepmc.org/articles/PMC8709900?pdf=render" }, + { + "id": "35997000", + "doi": "https://doi.org/10.1111/ene.15530", + "title": "Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.", + "authorString": "Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.", + "authorAffiliations": "", + "journalTitle": "European journal of neurology", + "pubYear": "2022", + "date": "2022-09-11", + "isOpenAccess": "Y", + "keywords": "Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and purpose

Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.

Methods

A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.

Results

Individuals with idiopathic dystonia (n\u00a0=\u200952,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n\u00a0=\u2009216,754, 43% vs. 31%, p\u00a0<\u20090.001; 45% vs. 37.9%, p\u00a0<\u20090.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR]\u2009=\u20091.98, 95% confidence interval [CI]\u2009=\u20091.9-2.1), with an IRR of 12.4 (95% CI\u00a0=\u00a011.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR\u00a0=\u00a01.96, 95% CI\u00a0=\u00a01.85-2.07).

Conclusions

This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render" + }, { "id": "35813279", "doi": "https://doi.org/10.1016/s2666-7568(22)00147-7", @@ -7530,6 +7547,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render" }, + { + "id": "33939953", + "doi": "https://doi.org/10.1016/s0140-6736(21)00634-6", + "title": "Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.", + "authorString": "Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, Eggo RM, Bhaskaran K, Wong AYS, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJW, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B, OpenSAFELY Collaborative.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2021", + "date": "2021-04-30", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

Methods

We conducted an observational cohort study of adults (aged \u226518 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.

Findings

Of 17\u2009288\u2009532 adults included in the study (excluding care home residents), 10\u2009877\u2009978 (62\u00b79%) were White, 1\u2009025\u2009319 (5\u00b79%) were South Asian, 340\u2009912 (2\u00b70%) were Black, 170\u2009484 (1\u00b70%) were of mixed ethnicity, 320\u2009788 (1\u00b79%) were of other ethnicity, and 4\u2009553\u2009051 (26\u00b73%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1\u00b708 [95% CI 1\u00b707-1\u00b709]), Black group (1\u00b708 [1\u00b706-1\u00b709]), and mixed ethnicity group (1\u00b704 [1\u00b702-1\u00b705]) and was decreased in the other ethnicity group (0\u00b777 [0\u00b776-0\u00b778]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1\u00b799 [1\u00b794-2\u00b704]), Black group (1\u00b769 [1\u00b762-1\u00b777]), mixed ethnicity group (1\u00b749 [1\u00b739-1\u00b759]), and other ethnicity group (1\u00b720 [1\u00b714-1\u00b728]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1\u00b748 [1\u00b741-1\u00b755], Black group 1\u00b778 [1\u00b767-1\u00b790], mixed ethnicity group 1\u00b763 [1\u00b745-1\u00b783], other ethnicity group 1\u00b754 [1\u00b741-1\u00b769]), COVID-19-related ICU admission (2\u00b718 [1\u00b792-2\u00b748], 3\u00b712 [2\u00b765-3\u00b767], 2\u00b796 [2\u00b726-3\u00b787], 3\u00b718 [2\u00b758-3\u00b793]), and death (1\u00b726 [1\u00b715-1\u00b737], 1\u00b751 [1\u00b731-1\u00b771], 1\u00b741 [1\u00b711-1\u00b781], 1\u00b722 [1\u00b700-1\u00b748]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.

Interpretation

Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.

Funding

Medical Research Council.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render" + }, { "id": "34837975", "doi": "https://doi.org/10.1186/s12885-021-09014-w", @@ -7548,21 +7582,21 @@ "urls": "doi:https://doi.org/10.1186/s12885-021-09014-w; html:https://europepmc.org/articles/PMC8626898; pdf:https://europepmc.org/articles/PMC8626898?pdf=render" }, { - "id": "33939953", - "doi": "https://doi.org/10.1016/s0140-6736(21)00634-6", - "title": "Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.", - "authorString": "Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, Eggo RM, Bhaskaran K, Wong AYS, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJW, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B, OpenSAFELY Collaborative.", + "id": "33644411", + "doi": "https://doi.org/10.23889/ijpds.v5i1.1346", + "title": "Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales: A Retrospective Review.", + "authorString": "Griffiths R, Schl\u00fcter DK, Akbari A, Cosgriff R, Tucker D, Taylor-Robinson D.", "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2021", - "date": "2021-04-30", + "journalTitle": "International journal of population data science", + "pubYear": "2020", + "date": "2020-08-11", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

Methods

We conducted an observational cohort study of adults (aged \u226518 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.

Findings

Of 17\u2009288\u2009532 adults included in the study (excluding care home residents), 10\u2009877\u2009978 (62\u00b79%) were White, 1\u2009025\u2009319 (5\u00b79%) were South Asian, 340\u2009912 (2\u00b70%) were Black, 170\u2009484 (1\u00b70%) were of mixed ethnicity, 320\u2009788 (1\u00b79%) were of other ethnicity, and 4\u2009553\u2009051 (26\u00b73%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1\u00b708 [95% CI 1\u00b707-1\u00b709]), Black group (1\u00b708 [1\u00b706-1\u00b709]), and mixed ethnicity group (1\u00b704 [1\u00b702-1\u00b705]) and was decreased in the other ethnicity group (0\u00b777 [0\u00b776-0\u00b778]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1\u00b799 [1\u00b794-2\u00b704]), Black group (1\u00b769 [1\u00b762-1\u00b777]), mixed ethnicity group (1\u00b749 [1\u00b739-1\u00b759]), and other ethnicity group (1\u00b720 [1\u00b714-1\u00b728]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1\u00b748 [1\u00b741-1\u00b755], Black group 1\u00b778 [1\u00b767-1\u00b790], mixed ethnicity group 1\u00b763 [1\u00b745-1\u00b783], other ethnicity group 1\u00b754 [1\u00b741-1\u00b769]), COVID-19-related ICU admission (2\u00b718 [1\u00b792-2\u00b748], 3\u00b712 [2\u00b765-3\u00b767], 2\u00b796 [2\u00b726-3\u00b787], 3\u00b718 [2\u00b758-3\u00b793]), and death (1\u00b726 [1\u00b715-1\u00b737], 1\u00b751 [1\u00b731-1\u00b771], 1\u00b741 [1\u00b711-1\u00b781], 1\u00b722 [1\u00b700-1\u00b748]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.

Interpretation

Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.

Funding

Medical Research Council.", + "abstract": "

Introduction

The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry.

Objectives

To establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research.

Methods

Three EHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications.

Results

We identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source.

Conclusion

Identifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render" + "urls": "doi:https://doi.org/10.23889/ijpds.v5i1.1346; html:https://europepmc.org/articles/PMC7898022; pdf:https://europepmc.org/articles/PMC7898022?pdf=render" }, { "id": "36434299", @@ -7581,23 +7615,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render" }, - { - "id": "33644411", - "doi": "https://doi.org/10.23889/ijpds.v5i1.1346", - "title": "Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales: A Retrospective Review.", - "authorString": "Griffiths R, Schl\u00fcter DK, Akbari A, Cosgriff R, Tucker D, Taylor-Robinson D.", - "authorAffiliations": "", - "journalTitle": "International journal of population data science", - "pubYear": "2020", - "date": "2020-08-11", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry.

Objectives

To establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research.

Methods

Three EHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications.

Results

We identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source.

Conclusion

Identifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.", - "laySummary": "", - "urls": "doi:https://doi.org/10.23889/ijpds.v5i1.1346; html:https://europepmc.org/articles/PMC7898022; pdf:https://europepmc.org/articles/PMC7898022?pdf=render" - }, { "id": "33965593", "doi": "https://doi.org/10.1016/j.jaip.2021.04.055", @@ -7766,7 +7783,7 @@ "healthCategories": "", "abstract": "

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably\u00a0that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is,\u00a0however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.", "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render" + "urls": "doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render; pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3" }, { "id": "37398988", @@ -7819,23 +7836,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ofid/ofac694; html:https://europepmc.org/articles/PMC9874026; pdf:https://europepmc.org/articles/PMC9874026?pdf=render" }, - { - "id": "35067242", - "doi": "https://doi.org/10.1192/bjp.2021.219", - "title": "Prediction models in first-episode psychosis: systematic review and critical appraisal.", - "authorString": "Lee R, Leighton SP, Thomas L, Gkoutos GV, Wood SJ, Fenton SH, Deligianni F, Cavanagh J, Mallikarjun PK.", - "authorAffiliations": "", - "journalTitle": "The British journal of psychiatry : the journal of mental science", - "pubYear": "2022", - "date": "2022-01-24", - "isOpenAccess": "N", - "keywords": "Prediction; Schizophrenia; Psychotic Disorders; Outcome Studies; Precision Medicine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.

Aims

We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.

Method

A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.

Results

Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.

Conclusions

Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1192/bjp.2021.219; html:https://europepmc.org/articles/PMC7612705; pdf:https://europepmc.org/articles/PMC7612705?pdf=render; doi:https://doi.org/10.1192/bjp.2021.219" - }, { "id": "33419870", "doi": "https://doi.org/10.1136/bmjhci-2020-100254", @@ -7870,6 +7870,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/cid/ciab159; html:https://europepmc.org/articles/PMC8599204; pdf:https://europepmc.org/articles/PMC8599204?pdf=render" }, + { + "id": "35067242", + "doi": "https://doi.org/10.1192/bjp.2021.219", + "title": "Prediction models in first-episode psychosis: systematic review and critical appraisal.", + "authorString": "Lee R, Leighton SP, Thomas L, Gkoutos GV, Wood SJ, Fenton SH, Deligianni F, Cavanagh J, Mallikarjun PK.", + "authorAffiliations": "", + "journalTitle": "The British journal of psychiatry : the journal of mental science", + "pubYear": "2022", + "date": "2022-01-24", + "isOpenAccess": "N", + "keywords": "Prediction; Schizophrenia; Psychotic Disorders; Outcome Studies; Precision Medicine", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.

Aims

We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.

Method

A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.

Results

Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.

Conclusions

Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1192/bjp.2021.219; html:https://europepmc.org/articles/PMC7612705; pdf:https://europepmc.org/articles/PMC7612705?pdf=render; doi:https://doi.org/10.1192/bjp.2021.219" + }, { "id": "33495722", "doi": "https://doi.org/10.1109/access.2021.3050524", @@ -7955,23 +7972,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41597-023-01949-y; html:https://europepmc.org/articles/PMC9887579; pdf:https://europepmc.org/articles/PMC9887579?pdf=render" }, - { - "id": "35534084", - "doi": "https://doi.org/10.1136/bmjopen-2021-054186", - "title": "Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.", - "authorString": "Gordon B, Fennessy C, Varma S, Barrett J, McCondochie E, Heritage T, Duroe O, Jeffery R, Rajamani V, Earlam K, Banda V, Sebire N.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-05-09", - "isOpenAccess": "Y", - "keywords": "Information management; information technology; Health Informatics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To objectively evaluate freely available data profiling software tools using healthcare data.

Design

Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset.

Setting

Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise.

Participants

28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients.

Results

Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics.

Conclusions

Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render" - }, { "id": "34164795", "doi": "https://doi.org/10.1007/s40801-021-00256-5", @@ -7990,21 +7990,21 @@ "urls": "doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf" }, { - "id": "35958702", - "doi": "https://doi.org/10.1007/s40653-021-00433-2", - "title": "The Secondary Harms of Parental Substance Use on Children's Educational Outcomes: A Review.", - "authorString": "Lowthian E.", + "id": "35534084", + "doi": "https://doi.org/10.1136/bmjopen-2021-054186", + "title": "Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.", + "authorString": "Gordon B, Fennessy C, Varma S, Barrett J, McCondochie E, Heritage T, Duroe O, Jeffery R, Rajamani V, Earlam K, Banda V, Sebire N.", "authorAffiliations": "", - "journalTitle": "Journal of child & adolescent trauma", + "journalTitle": "BMJ open", "pubYear": "2022", - "date": "2022-01-14", + "date": "2022-05-09", "isOpenAccess": "Y", - "keywords": "Drugs; Review; Alcohol; Education; Parental Substance Use", + "keywords": "Information management; information technology; Health Informatics", "nationalPriorities": "", "healthCategories": "", - "abstract": "Parental substance use, that is alcohol and illicit drugs, can have\u00a0a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current\u00a0reviews of the literature in the field\u00a0of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's\u00a0educational attainment. To grasp the available literature, the method from Arksey and O'Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children's school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children's educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.", + "abstract": "

Objectives

To objectively evaluate freely available data profiling software tools using healthcare data.

Design

Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset.

Setting

Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise.

Participants

28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients.

Results

Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics.

Conclusions

Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.", "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s40653-021-00433-2; html:https://europepmc.org/articles/PMC9360289; pdf:https://europepmc.org/articles/PMC9360289?pdf=render" + "urls": "doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render" }, { "id": "31591592", @@ -8023,6 +8023,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41591-019-0597-x; html:https://europepmc.org/articles/PMC7076561; pdf:https://europepmc.org/articles/PMC7076561?pdf=render; doi:https://doi.org/10.1038/s41591-019-0597-x" }, + { + "id": "35958702", + "doi": "https://doi.org/10.1007/s40653-021-00433-2", + "title": "The Secondary Harms of Parental Substance Use on Children's Educational Outcomes: A Review.", + "authorString": "Lowthian E.", + "authorAffiliations": "", + "journalTitle": "Journal of child & adolescent trauma", + "pubYear": "2022", + "date": "2022-01-14", + "isOpenAccess": "Y", + "keywords": "Drugs; Review; Alcohol; Education; Parental Substance Use", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Parental substance use, that is alcohol and illicit drugs, can have\u00a0a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current\u00a0reviews of the literature in the field\u00a0of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's\u00a0educational attainment. To grasp the available literature, the method from Arksey and O'Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children's school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children's educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s40653-021-00433-2; html:https://europepmc.org/articles/PMC9360289; pdf:https://europepmc.org/articles/PMC9360289?pdf=render" + }, { "id": "37649988", "doi": "https://doi.org/10.1093/jamiaopen/ooad078", @@ -8210,23 +8227,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/genes12111758; html:https://europepmc.org/articles/PMC8620997; pdf:https://europepmc.org/articles/PMC8620997?pdf=render" }, - { - "id": "37080566", - "doi": "https://doi.org/10.1183/13993003.01720-2022", - "title": "Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.", - "authorString": "Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Mois\u00e9s J, Pech\u00e9 R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.", - "authorAffiliations": "", - "journalTitle": "The European respiratory journal", - "pubYear": "2023", - "date": "2023-05-18", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render" - }, { "id": "34071236", "doi": "https://doi.org/10.3390/ijms22115763", @@ -8244,6 +8244,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijms22115763; html:https://europepmc.org/articles/PMC8198673; pdf:https://europepmc.org/articles/PMC8198673?pdf=render" }, + { + "id": "37080566", + "doi": "https://doi.org/10.1183/13993003.01720-2022", + "title": "Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.", + "authorString": "Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Mois\u00e9s J, Pech\u00e9 R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.", + "authorAffiliations": "", + "journalTitle": "The European respiratory journal", + "pubYear": "2023", + "date": "2023-05-18", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render" + }, { "id": "36680646", "doi": "https://doi.org/10.1007/s10654-022-00962-6", @@ -8312,23 +8329,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render" }, - { - "id": "36753492", - "doi": "https://doi.org/10.1371/journal.pone.0281466", - "title": "Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.", - "authorString": "Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-02-08", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.

Methods

We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.

Results

In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.

Conclusions

Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable" - }, { "id": "35845286", "doi": "https://doi.org/10.1002/jha2.182", @@ -8346,6 +8346,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/jha2.182; html:https://europepmc.org/articles/PMC9175663; pdf:https://europepmc.org/articles/PMC9175663?pdf=render" }, + { + "id": "36753492", + "doi": "https://doi.org/10.1371/journal.pone.0281466", + "title": "Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.", + "authorString": "Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-02-08", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.

Methods

We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.

Results

In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.

Conclusions

Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable" + }, { "id": "36329425", "doi": "https://doi.org/10.1186/s12890-022-02189-3", @@ -8363,23 +8380,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render" }, - { - "id": "36073628", - "doi": "https://doi.org/10.1161/jaha.122.026432", - "title": "Differential Patterns and Outcomes of 20.6\u00a0Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.", - "authorString": "Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, Sharma G, Bullock-Palmer RP, Petersen SE, Mehta LS, Ullah W, Roguin A, Sun LY, Mamas MA.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2022", - "date": "2022-09-08", - "isOpenAccess": "Y", - "keywords": "Men; Essential hypertension; Atrial fibrillation; Stroke; Women; Sex characteristics; United States", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background We describe sex-differential disease patterns and outcomes of >20.6\u00a0million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?pdf=render" - }, { "id": "35836669", "doi": "https://doi.org/10.1097/txd.0000000000001188", @@ -8397,6 +8397,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render" }, + { + "id": "36073628", + "doi": "https://doi.org/10.1161/jaha.122.026432", + "title": "Differential Patterns and Outcomes of 20.6\u00a0Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.", + "authorString": "Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, Sharma G, Bullock-Palmer RP, Petersen SE, Mehta LS, Ullah W, Roguin A, Sun LY, Mamas MA.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2022", + "date": "2022-09-08", + "isOpenAccess": "Y", + "keywords": "Men; Essential hypertension; Atrial fibrillation; Stroke; Women; Sex characteristics; United States", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background We describe sex-differential disease patterns and outcomes of >20.6\u00a0million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?pdf=render" + }, { "id": "35531432", "doi": "https://doi.org/10.1016/s2666-7568(22)00093-9", @@ -8482,23 +8499,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/archdischild-2022-324713; html:https://europepmc.org/articles/PMC10313998; pdf:https://europepmc.org/articles/PMC10313998?pdf=render" }, - { - "id": "36384749", - "doi": "https://doi.org/10.1136/heartjnl-2022-321733", - "title": "Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.", - "authorString": "Raisi-Estabragh Z, Cooper J, Bethell MS, McCracken C, Lewandowski AJ, Leeson P, Neubauer S, Harvey NC, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Heart (British Cardiac Society)", - "pubYear": "2023", - "date": "2023-03-10", - "isOpenAccess": "Y", - "keywords": "epidemiology; Magnetic Resonance Imaging; risk factors", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.

Methods

Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.

Results

258\u2009787 participants from white ethnicities (61%\u2009women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2\u2009kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0\u00d710-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19\u2009314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).

Conclusions

Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render" - }, { "id": "35443953", "doi": "https://doi.org/10.1136/bmjopen-2021-056523", @@ -8516,6 +8516,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render" }, + { + "id": "36384749", + "doi": "https://doi.org/10.1136/heartjnl-2022-321733", + "title": "Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.", + "authorString": "Raisi-Estabragh Z, Cooper J, Bethell MS, McCracken C, Lewandowski AJ, Leeson P, Neubauer S, Harvey NC, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "Heart (British Cardiac Society)", + "pubYear": "2023", + "date": "2023-03-10", + "isOpenAccess": "Y", + "keywords": "epidemiology; Magnetic Resonance Imaging; risk factors", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.

Methods

Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.

Results

258\u2009787 participants from white ethnicities (61%\u2009women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2\u2009kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0\u00d710-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19\u2009314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).

Conclusions

Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render" + }, { "id": "33185672", "doi": "https://doi.org/10.1093/jamia/ocaa295", @@ -8754,6 +8771,23 @@ "laySummary": "Vespignani et al. used mathematical models to model the epidemic of covid-19 and to predict future scenarios for possible interventions and inform policy and practice.", "urls": "doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render" }, + { + "id": "35814295", + "doi": "https://doi.org/10.1038/s43856-022-00146-z", + "title": "Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.", + "authorString": "Wong NCK, Meshkinfamfard S, Turb\u00e9 V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka RJ, Cooke GS, McKendry RA, Atchison CJ, Bharath AA.", + "authorAffiliations": "", + "journalTitle": "Communications medicine", + "pubYear": "2022", + "date": "2022-07-06", + "isOpenAccess": "Y", + "keywords": "Databases; Public Health", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.

Methods

Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.

Results

Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).

Conclusions

Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render" + }, { "id": "36921925", "doi": "https://doi.org/10.1136/bmj-2022-072808", @@ -8788,23 +8822,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-022-35017-7; html:https://europepmc.org/articles/PMC9708841; pdf:https://europepmc.org/articles/PMC9708841?pdf=render" }, - { - "id": "35814295", - "doi": "https://doi.org/10.1038/s43856-022-00146-z", - "title": "Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.", - "authorString": "Wong NCK, Meshkinfamfard S, Turb\u00e9 V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka RJ, Cooke GS, McKendry RA, Atchison CJ, Bharath AA.", - "authorAffiliations": "", - "journalTitle": "Communications medicine", - "pubYear": "2022", - "date": "2022-07-06", - "isOpenAccess": "Y", - "keywords": "Databases; Public Health", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.

Methods

Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.

Results

Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).

Conclusions

Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render" - }, { "id": "36541282", "doi": "https://doi.org/10.14814/phy2.15546", @@ -8822,23 +8839,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render" }, - { - "id": "37561116", - "doi": "https://doi.org/10.7554/elife.85332", - "title": "Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP.", - "authorString": "Lemanska A, Andrews C, Fisher L, Bacon S, Frampton AE, Mehrkar A, Inglesby P, Davy S, Roberts K, Patalay P, Goldacre B, MacKenna B, OpenSAFELY Collaborative, Walker AJ.", - "authorAffiliations": "", - "journalTitle": "eLife", - "pubYear": "2023", - "date": "2023-08-10", - "isOpenAccess": "Y", - "keywords": "Human; Pancreatic cancer; epidemiology; Global Health; Healthcare; Healthcare Crisis; Covid-19; Healthcare Disruption", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic.

Methods

With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates.

Results

The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (\u00b111 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital admissions, and deaths were not affected.

Conclusions

The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.

Funding

This work was jointly funded by the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). This work was funded by Medical Research Council (MRC) grant reference MR/W021390/1 as part of the postdoctoral fellowship awarded to AL and undertaken at the Bennett Institute, University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UKHSA), or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.", - "laySummary": "", - "urls": "doi:https://doi.org/10.7554/eLife.85332; html:https://europepmc.org/articles/PMC10414967; pdf:https://europepmc.org/articles/PMC10414967?pdf=render" - }, { "id": "33632765", "doi": "https://doi.org/10.1136/thoraxjnl-2020-215986", @@ -8856,6 +8856,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render" }, + { + "id": "37561116", + "doi": "https://doi.org/10.7554/elife.85332", + "title": "Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP.", + "authorString": "Lemanska A, Andrews C, Fisher L, Bacon S, Frampton AE, Mehrkar A, Inglesby P, Davy S, Roberts K, Patalay P, Goldacre B, MacKenna B, OpenSAFELY Collaborative, Walker AJ.", + "authorAffiliations": "", + "journalTitle": "eLife", + "pubYear": "2023", + "date": "2023-08-10", + "isOpenAccess": "Y", + "keywords": "Human; Pancreatic cancer; epidemiology; Global Health; Healthcare; Healthcare Crisis; Covid-19; Healthcare Disruption", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic.

Methods

With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates.

Results

The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (\u00b111 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital admissions, and deaths were not affected.

Conclusions

The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.

Funding

This work was jointly funded by the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). This work was funded by Medical Research Council (MRC) grant reference MR/W021390/1 as part of the postdoctoral fellowship awarded to AL and undertaken at the Bennett Institute, University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UKHSA), or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.", + "laySummary": "", + "urls": "doi:https://doi.org/10.7554/eLife.85332; html:https://europepmc.org/articles/PMC10414967; pdf:https://europepmc.org/articles/PMC10414967?pdf=render" + }, { "id": "36374585", "doi": "https://doi.org/10.1177/01410768221131897", @@ -9094,6 +9111,23 @@ "laySummary": "This retrospective observational cohort study aimed to quanitfy the number of patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin who exhibit NICE-defined poor international normalised ratio (INR) control. Another objective was to describe the relationship between demographic and clinical characteristics of these patients and poor INR control. The results from statistical analyses in this study suggest a considerable opportunity to improve both embloc and bleeding risk, eben though the relationship between poor INR control and these clinical outcomes remains to be determined.", "urls": "doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?pdf=render" }, + { + "id": "35879616", + "doi": "https://doi.org/10.1038/s41591-022-01909-w", + "title": "Symptoms and risk factors for long COVID in non-hospitalized adults.", + "authorString": "Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2022", + "date": "2022-07-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render; pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf" + }, { "id": "34894331", "doi": "https://doi.org/10.1007/s10461-021-03551-y", @@ -9112,21 +9146,21 @@ "urls": "doi:https://doi.org/10.1007/s10461-021-03551-y; html:https://europepmc.org/articles/PMC9046343; pdf:https://europepmc.org/articles/PMC9046343?pdf=render" }, { - "id": "35879616", - "doi": "https://doi.org/10.1038/s41591-022-01909-w", - "title": "Symptoms and risk factors for long COVID in non-hospitalized adults.", - "authorString": "Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.", + "id": "37118449", + "doi": "https://doi.org/10.1038/s43587-022-00224-w", + "title": "Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-na\u00efve residents of long-term care facilities who survive natural infection.", + "authorString": "Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.", "authorAffiliations": "", - "journalTitle": "Nature medicine", + "journalTitle": "Nature aging", "pubYear": "2022", - "date": "2022-07-25", + "date": "2022-05-30", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.", + "abstract": "We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render; pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf" + "urls": "doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render" }, { "id": "36933612", @@ -9145,23 +9179,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.cct.2023.107162" }, - { - "id": "37118449", - "doi": "https://doi.org/10.1038/s43587-022-00224-w", - "title": "Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-na\u00efve residents of long-term care facilities who survive natural infection.", - "authorString": "Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.", - "authorAffiliations": "", - "journalTitle": "Nature aging", - "pubYear": "2022", - "date": "2022-05-30", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render" - }, { "id": "35256633", "doi": "https://doi.org/10.1038/s41598-022-07291-4", @@ -9247,23 +9264,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12874-023-02000-9" }, - { - "id": "36874571", - "doi": "https://doi.org/10.12688/wellcomeopenres.17981.1", - "title": "Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.", - "authorString": "Hoskins S, Beale S, Nguyen V, Fragaszy E, Navaratnam AMD, Smith C, French C, Kovar J, Byrne T, Fong WLE, Geismar C, Patel P, Yavlinksy A, Johnson AM, Aldridge RW, Hayward A, Virus Watch Collaborative.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2022", - "date": "2022-08-03", - "isOpenAccess": "Y", - "keywords": "Transmission; Activities; Pandemic; Work; Public Transport; Shopping; Lockdown; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: \"Lockdowns\" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.\u00a0 However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.\u00a0 Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.\u00a0 Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.\u00a0 We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.\u00a0 Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).\u00a0 Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.\u00a0 Most participants visited shops, accounting for one-third of non-household transmission. \u00a0Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.\u00a0 \u00a0If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17981.1; html:https://europepmc.org/articles/PMC9975411; pdf:https://europepmc.org/articles/PMC9975411?pdf=render" - }, { "id": "35308936", "doi": "https://doi.org/", @@ -9281,6 +9281,23 @@ "laySummary": "", "urls": "html:https://europepmc.org/articles/PMC8861677; pdf:https://europepmc.org/articles/PMC8861677?pdf=render" }, + { + "id": "36874571", + "doi": "https://doi.org/10.12688/wellcomeopenres.17981.1", + "title": "Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.", + "authorString": "Hoskins S, Beale S, Nguyen V, Fragaszy E, Navaratnam AMD, Smith C, French C, Kovar J, Byrne T, Fong WLE, Geismar C, Patel P, Yavlinksy A, Johnson AM, Aldridge RW, Hayward A, Virus Watch Collaborative.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2022", + "date": "2022-08-03", + "isOpenAccess": "Y", + "keywords": "Transmission; Activities; Pandemic; Work; Public Transport; Shopping; Lockdown; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: \"Lockdowns\" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.\u00a0 However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.\u00a0 Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.\u00a0 Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.\u00a0 We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.\u00a0 Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).\u00a0 Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.\u00a0 Most participants visited shops, accounting for one-third of non-household transmission. \u00a0Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.\u00a0 \u00a0If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17981.1; html:https://europepmc.org/articles/PMC9975411; pdf:https://europepmc.org/articles/PMC9975411?pdf=render" + }, { "id": "36994768", "doi": "https://doi.org/10.1002/cphy.c210037", @@ -9519,23 +9536,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render" }, - { - "id": "36808078", - "doi": "https://doi.org/10.1136/pn-2021-003286", - "title": "Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.", - "authorString": "Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.", - "authorAffiliations": "", - "journalTitle": "Practical neurology", - "pubYear": "2023", - "date": "2023-02-20", - "isOpenAccess": "Y", - "keywords": "Clinical Neurology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render; pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf" - }, { "id": "35485805", "doi": "https://doi.org/10.1017/s003329172200109x", @@ -9553,6 +9553,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?pdf=render; pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/BDE3DC6059EB59B00B2E0CD892963804/S003329172200109Xa.pdf/div-class-title-multimorbidity-clusters-among-people-with-serious-mental-illness-a-representative-primary-and-secondary-data-linkage-cohort-study-div.pdf" }, + { + "id": "36808078", + "doi": "https://doi.org/10.1136/pn-2021-003286", + "title": "Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.", + "authorString": "Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.", + "authorAffiliations": "", + "journalTitle": "Practical neurology", + "pubYear": "2023", + "date": "2023-02-20", + "isOpenAccess": "Y", + "keywords": "Clinical Neurology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render; pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf" + }, { "id": "34308306", "doi": "https://doi.org/10.1016/j.eclinm.2021.100888", @@ -9604,6 +9621,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render" }, + { + "id": "35996157", + "doi": "https://doi.org/10.1186/s13059-022-02745-4", + "title": "Comparative transcriptome in large-scale human and cattle populations.", + "authorString": "Yao Y, Liu S, Xia C, Gao Y, Pan Z, Canela-Xandri O, Khamseh A, Rawlik K, Wang S, Li B, Zhang Y, Pairo-Castineira E, D'Mellow K, Li X, Yan Z, Li CJ, Yu Y, Zhang S, Ma L, Cole JB, Ross PJ, Zhou H, Haley C, Liu GE, Fang L, Tenesa A.", + "authorAffiliations": "", + "journalTitle": "Genome biology", + "pubYear": "2022", + "date": "2022-08-22", + "isOpenAccess": "Y", + "keywords": "Rna-seq; Gene Co-expression; Comparative Transcriptome; Inter-individual Variability; Heritability Enrichment", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes.

Results

Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues.

Conclusions

In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13059-022-02745-4; html:https://europepmc.org/articles/PMC9394047; pdf:https://europepmc.org/articles/PMC9394047?pdf=render" + }, { "id": "37526977", "doi": "https://doi.org/10.5830/cvja-2023-037", @@ -9638,23 +9672,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/trf.17277; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277" }, - { - "id": "35996157", - "doi": "https://doi.org/10.1186/s13059-022-02745-4", - "title": "Comparative transcriptome in large-scale human and cattle populations.", - "authorString": "Yao Y, Liu S, Xia C, Gao Y, Pan Z, Canela-Xandri O, Khamseh A, Rawlik K, Wang S, Li B, Zhang Y, Pairo-Castineira E, D'Mellow K, Li X, Yan Z, Li CJ, Yu Y, Zhang S, Ma L, Cole JB, Ross PJ, Zhou H, Haley C, Liu GE, Fang L, Tenesa A.", - "authorAffiliations": "", - "journalTitle": "Genome biology", - "pubYear": "2022", - "date": "2022-08-22", - "isOpenAccess": "Y", - "keywords": "Rna-seq; Gene Co-expression; Comparative Transcriptome; Inter-individual Variability; Heritability Enrichment", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes.

Results

Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues.

Conclusions

In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13059-022-02745-4; html:https://europepmc.org/articles/PMC9394047; pdf:https://europepmc.org/articles/PMC9394047?pdf=render" - }, { "id": "36377225", "doi": "https://doi.org/10.1177/18333583221135710", @@ -9689,23 +9706,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-052911; html:https://europepmc.org/articles/PMC8852656; pdf:https://europepmc.org/articles/PMC8852656?pdf=render" }, - { - "id": "37381004", - "doi": "https://doi.org/10.1186/s12913-023-09545-x", - "title": "A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.", - "authorString": "Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.", - "authorAffiliations": "", - "journalTitle": "BMC health services research", - "pubYear": "2023", - "date": "2023-06-28", - "isOpenAccess": "Y", - "keywords": "Trauma; Rural; Interview; Older Adults", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render" - }, { "id": "34007896", "doi": "https://doi.org/10.23889/ijpds.v6i1.1387", @@ -9723,6 +9723,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render" }, + { + "id": "37381004", + "doi": "https://doi.org/10.1186/s12913-023-09545-x", + "title": "A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.", + "authorString": "Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.", + "authorAffiliations": "", + "journalTitle": "BMC health services research", + "pubYear": "2023", + "date": "2023-06-28", + "isOpenAccess": "Y", + "keywords": "Trauma; Rural; Interview; Older Adults", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render" + }, { "id": "34148732", "doi": "https://doi.org/10.1016/j.bja.2021.05.001", @@ -9757,23 +9774,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render" }, - { - "id": "36567336", - "doi": "https://doi.org/10.1186/s12872-022-03005-w", - "title": "Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.", - "authorString": "Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.", - "authorAffiliations": "", - "journalTitle": "BMC cardiovascular disorders", - "pubYear": "2022", - "date": "2022-12-26", - "isOpenAccess": "Y", - "keywords": "Dyspnea; Machine Learning; Hfpef", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a\u00a0data-driven diagnostic\u00a0model\u00a0to\u00a0predict\u00a0from electronic health records (EHR) the likelihood of\u00a0HFpEF\u00a0among patients with\u00a0unexplained dyspnea and preserved left ventricular EF.

Methods and results

The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF\u00a0(cases), non-HF (control\u00a0cohort I),\u00a0or\u00a0HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting\u00a0HFpEF had an AUROC of 90% (P\u2009<\u20090.001) and average precision of 74%.

Conclusion

This diagnostic signature enables discrimination of\u00a0HFpEF\u00a0from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with\u00a0unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render" - }, { "id": "34534697", "doi": "https://doi.org/10.1016/j.jbi.2021.103916", @@ -9791,6 +9791,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jbi.2021.103916; html:https://europepmc.org/articles/PMC8524321" }, + { + "id": "36567336", + "doi": "https://doi.org/10.1186/s12872-022-03005-w", + "title": "Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.", + "authorString": "Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.", + "authorAffiliations": "", + "journalTitle": "BMC cardiovascular disorders", + "pubYear": "2022", + "date": "2022-12-26", + "isOpenAccess": "Y", + "keywords": "Dyspnea; Machine Learning; Hfpef", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a\u00a0data-driven diagnostic\u00a0model\u00a0to\u00a0predict\u00a0from electronic health records (EHR) the likelihood of\u00a0HFpEF\u00a0among patients with\u00a0unexplained dyspnea and preserved left ventricular EF.

Methods and results

The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF\u00a0(cases), non-HF (control\u00a0cohort I),\u00a0or\u00a0HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting\u00a0HFpEF had an AUROC of 90% (P\u2009<\u20090.001) and average precision of 74%.

Conclusion

This diagnostic signature enables discrimination of\u00a0HFpEF\u00a0from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with\u00a0unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render" + }, { "id": "35813280", "doi": "https://doi.org/10.1016/s2666-7568(22)00118-0", @@ -10080,23 +10097,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1007/s10654-021-00722-y; html:https://europepmc.org/articles/PMC7882869; pdf:https://europepmc.org/articles/PMC7882869?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00722-y.pdf" }, - { - "id": "37635632", - "doi": "https://doi.org/10.1111/aor.14628", - "title": "Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.", - "authorString": "Numan L, W\u00f6sten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.", - "authorAffiliations": "", - "journalTitle": "Artificial organs", - "pubYear": "2023", - "date": "2023-08-28", - "isOpenAccess": "N", - "keywords": "Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).

Methods

18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2\u2009weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.

Results

A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p\u2009<\u20090.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p\u2009<\u20090.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p\u2009=\u20090.19).

Conclusions

A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1111/aor.14628" - }, { "id": "34249083", "doi": "https://doi.org/10.3389/fgene.2021.652878", @@ -10132,21 +10132,21 @@ "urls": "doi:https://doi.org/10.1210/clinem/dgac527; html:https://europepmc.org/articles/PMC9693767" }, { - "id": "35216844", - "doi": "https://doi.org/10.1016/j.vaccine.2022.02.056", - "title": "Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.", - "authorString": "Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NRH, Lal S, Eggo RM, Marks M, Chantler T.", + "id": "37635632", + "doi": "https://doi.org/10.1111/aor.14628", + "title": "Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.", + "authorString": "Numan L, W\u00f6sten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.", "authorAffiliations": "", - "journalTitle": "Vaccine", - "pubYear": "2022", - "date": "2022-02-17", - "isOpenAccess": "Y", - "keywords": "Qualitative Research; Ethnic Minorities; Coronavirus Vaccine; Localising Services; Public Health Collaboration", + "journalTitle": "Artificial organs", + "pubYear": "2023", + "date": "2023-08-28", + "isOpenAccess": "N", + "keywords": "Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters", "nationalPriorities": "", "healthCategories": "", - "abstract": "Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.", + "abstract": "

Background

Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).

Methods

18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2\u2009weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.

Results

A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p\u2009<\u20090.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p\u2009<\u20090.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p\u2009=\u20090.19).

Conclusions

A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863" + "urls": "doi:https://doi.org/10.1111/aor.14628" }, { "id": "33635829", @@ -10165,6 +10165,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render" }, + { + "id": "35216844", + "doi": "https://doi.org/10.1016/j.vaccine.2022.02.056", + "title": "Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.", + "authorString": "Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NRH, Lal S, Eggo RM, Marks M, Chantler T.", + "authorAffiliations": "", + "journalTitle": "Vaccine", + "pubYear": "2022", + "date": "2022-02-17", + "isOpenAccess": "Y", + "keywords": "Qualitative Research; Ethnic Minorities; Coronavirus Vaccine; Localising Services; Public Health Collaboration", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863" + }, { "id": "35580876", "doi": "https://doi.org/10.1136/bmj-2021-069704", @@ -10199,23 +10216,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00147-9; html:https://europepmc.org/articles/PMC9489064; pdf:https://europepmc.org/articles/PMC9489064?pdf=render" }, - { - "id": "36935397", - "doi": "https://doi.org/10.1093/bjs/znad055", - "title": "Validating a novel natural language processing pathway for automated quality assurance in surgical oncology: incomplete excision rates of 34 955 basal cell carcinomas.", - "authorString": "Ali SR, Dobbs TD, Jovic M, Strafford H, Fonferko-Shadrach B, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.", - "authorAffiliations": "", - "journalTitle": "The British journal of surgery", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/bjs/znad055; html:https://europepmc.org/articles/PMC10416688; pdf:https://europepmc.org/articles/PMC10416688?pdf=render; pdf:https://academic.oup.com/bjs/advance-article-pdf/doi/10.1093/bjs/znad055/49561408/znad055.pdf" - }, { "id": "37105743", "doi": "https://doi.org/10.3399/bjgp.2022.0353", @@ -10233,6 +10233,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render; pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf" }, + { + "id": "36935397", + "doi": "https://doi.org/10.1093/bjs/znad055", + "title": "Validating a novel natural language processing pathway for automated quality assurance in surgical oncology: incomplete excision rates of 34 955 basal cell carcinomas.", + "authorString": "Ali SR, Dobbs TD, Jovic M, Strafford H, Fonferko-Shadrach B, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "The British journal of surgery", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/bjs/znad055; html:https://europepmc.org/articles/PMC10416688; pdf:https://europepmc.org/articles/PMC10416688?pdf=render; pdf:https://academic.oup.com/bjs/advance-article-pdf/doi/10.1093/bjs/znad055/49561408/znad055.pdf" + }, { "id": "35079022", "doi": "https://doi.org/10.1038/s41467-022-28157-3", @@ -10318,23 +10335,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-054414; html:https://europepmc.org/articles/PMC8788233; pdf:https://europepmc.org/articles/PMC8788233?pdf=render" }, - { - "id": "37042240", - "doi": "https://doi.org/10.1161/circimaging.122.014519", - "title": "Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.", - "authorString": "Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Circulation. Cardiovascular imaging", - "pubYear": "2023", - "date": "2023-04-12", - "isOpenAccess": "N", - "keywords": "Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/CIRCIMAGING.122.014519" - }, { "id": "36764720", "doi": "https://doi.org/10.1136/bmjopen-2022-063836", @@ -10353,21 +10353,21 @@ "urls": "doi:https://doi.org/10.1136/bmjopen-2022-063836; html:https://europepmc.org/articles/PMC9923297; pdf:https://europepmc.org/articles/PMC9923297?pdf=render" }, { - "id": "34353320", - "doi": "https://doi.org/10.1186/s12916-021-02045-x", - "title": "Adverse childhood experiences and child mental health: an electronic birth cohort study.", - "authorString": "Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.", + "id": "37042240", + "doi": "https://doi.org/10.1161/circimaging.122.014519", + "title": "Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.", + "authorString": "Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.", "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2021", - "date": "2021-08-06", - "isOpenAccess": "Y", - "keywords": "Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences", + "journalTitle": "Circulation. Cardiovascular imaging", + "pubYear": "2023", + "date": "2023-04-12", + "isOpenAccess": "N", + "keywords": "Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders),\u00a0and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.", + "abstract": "Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.", "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render" + "urls": "doi:https://doi.org/10.1161/CIRCIMAGING.122.014519" }, { "id": "30950797", @@ -10386,6 +10386,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205" }, + { + "id": "34353320", + "doi": "https://doi.org/10.1186/s12916-021-02045-x", + "title": "Adverse childhood experiences and child mental health: an electronic birth cohort study.", + "authorString": "Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2021", + "date": "2021-08-06", + "isOpenAccess": "Y", + "keywords": "Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders),\u00a0and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render" + }, { "id": "36918541", "doi": "https://doi.org/10.1038/s41467-023-36997-w", @@ -10590,23 +10607,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-022-32095-5; html:https://europepmc.org/articles/PMC9363492; pdf:https://europepmc.org/articles/PMC9363492?pdf=render; pdf:https://www.nature.com/articles/s41467-022-32095-5.pdf" }, - { - "id": "35976089", - "doi": "https://doi.org/10.1515/cclm-2022-0135", - "title": "Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort.", - "authorString": "Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, Mills NL, O'Rahilly S, Sattar N.", - "authorAffiliations": "", - "journalTitle": "Clinical chemistry and laboratory medicine", - "pubYear": "2022", - "date": "2022-08-18", - "isOpenAccess": "N", - "keywords": "Biochemical markers; Guidelines; Reference Ranges", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Growth differentiation factor (GDF)-15 is attracting interest as a biomarker in several areas of medicine. We aimed to evaluate the reference range for GDF-15 in\u00a0a\u00a0general population, and to explore demographics, classical cardiovascular disease risk factors, and other cardiac biomarkers associated with GDF-15.

Methods

GDF-15 was measured in serum from 19,462 individuals in the Generation Scotland Scottish Family Health Study. Associations of cardiometabolic risk factors with GDF-15 were tested using adjusted linear regression. Among 18,507 participants with no heart disease, heart failure, or stroke, and not pregnant, reference ranges (median and 97.5th centiles) were derived by decade age bands and sex.

Results

Among males in the reference range population, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135)\u00a0pg/mL, rising to 931 (2,492)\u00a0pg/mL at 50-59\u00a0years, and 2,152 (5,972) pg/mL at\u00a0\u226580 years. In females, median GDF-15 at age <30\u00a0years was 628 (2,195)\u00a0pg/mL, 881 (2,323)\u00a0pg/mL at 50-59\u00a0years, and 1847 (6,830)\u00a0pg/mL at\u00a0\u226580\u00a0years. Among those known to be pregnant, median GDF-15 was 19,311\u00a0pg/mL. After adjustment, GDF-15 was\u00a0higher in participants with adverse cardiovascular risk factors, including current smoking (+26.1%), those with previous heart disease (+12.7%), stroke (+17.1%), heart failure (+25.3%), and particularly diabetes (+60.2%). GDF-15 had positive associations with cardiac biomarkers cardiac troponin I, cardiac troponin T, and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Conclusions

These data define reference ranges for GDF-15 for comparison in future studies, and identify potentially confounding risk factors and mediators to be considered in interpreting GDF-15 concentrations.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1515/cclm-2022-0135; html:https://europepmc.org/articles/PMC9524804; pdf:https://europepmc.org/articles/PMC9524804?pdf=render; doi:https://doi.org/10.1515/cclm-2022-0135" - }, { "id": "35786634", "doi": "https://doi.org/10.2196/37821", @@ -10624,6 +10624,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/37821; html:https://europepmc.org/articles/PMC9400842; pdf:https://europepmc.org/articles/PMC9400842?pdf=render" }, + { + "id": "35976089", + "doi": "https://doi.org/10.1515/cclm-2022-0135", + "title": "Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort.", + "authorString": "Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, Mills NL, O'Rahilly S, Sattar N.", + "authorAffiliations": "", + "journalTitle": "Clinical chemistry and laboratory medicine", + "pubYear": "2022", + "date": "2022-08-18", + "isOpenAccess": "N", + "keywords": "Biochemical markers; Guidelines; Reference Ranges", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Growth differentiation factor (GDF)-15 is attracting interest as a biomarker in several areas of medicine. We aimed to evaluate the reference range for GDF-15 in\u00a0a\u00a0general population, and to explore demographics, classical cardiovascular disease risk factors, and other cardiac biomarkers associated with GDF-15.

Methods

GDF-15 was measured in serum from 19,462 individuals in the Generation Scotland Scottish Family Health Study. Associations of cardiometabolic risk factors with GDF-15 were tested using adjusted linear regression. Among 18,507 participants with no heart disease, heart failure, or stroke, and not pregnant, reference ranges (median and 97.5th centiles) were derived by decade age bands and sex.

Results

Among males in the reference range population, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135)\u00a0pg/mL, rising to 931 (2,492)\u00a0pg/mL at 50-59\u00a0years, and 2,152 (5,972) pg/mL at\u00a0\u226580 years. In females, median GDF-15 at age <30\u00a0years was 628 (2,195)\u00a0pg/mL, 881 (2,323)\u00a0pg/mL at 50-59\u00a0years, and 1847 (6,830)\u00a0pg/mL at\u00a0\u226580\u00a0years. Among those known to be pregnant, median GDF-15 was 19,311\u00a0pg/mL. After adjustment, GDF-15 was\u00a0higher in participants with adverse cardiovascular risk factors, including current smoking (+26.1%), those with previous heart disease (+12.7%), stroke (+17.1%), heart failure (+25.3%), and particularly diabetes (+60.2%). GDF-15 had positive associations with cardiac biomarkers cardiac troponin I, cardiac troponin T, and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Conclusions

These data define reference ranges for GDF-15 for comparison in future studies, and identify potentially confounding risk factors and mediators to be considered in interpreting GDF-15 concentrations.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1515/cclm-2022-0135; html:https://europepmc.org/articles/PMC9524804; pdf:https://europepmc.org/articles/PMC9524804?pdf=render; doi:https://doi.org/10.1515/cclm-2022-0135" + }, { "id": "36543561", "doi": "https://doi.org/10.3399/bjgp.2022.0156", @@ -10709,6 +10726,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render" }, + { + "id": "37657941", + "doi": "https://doi.org/10.1212/wnl.0000000000207777", + "title": "Exploring the Role of Plasma Lipids and Statins Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.", + "authorString": "Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys RR, Chopade S, Hingorani AD, Wood NW.", + "authorAffiliations": "", + "journalTitle": "Neurology", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

There has been considerable interest in statins due to their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We employed two-sample Mendelian randomization (MR) to investigate: (1) the causal role of genetically mimic both cholesterol-dependent (via low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (via Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)) levels and MS risk and severity; and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n =7,069).

Results

The results of MR using the inverse variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway, (OR 0.86 (95% CI 0.78 to 0.95), p-value 3.80E-03) is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. MR results also show that lifelong higher HDL-C (OR 1.14 (95% CI 1.04 to1.26), p-value 7.94E-03) increase MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Conclusion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Since RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk via a cholesterol-independent pathway (i.e., RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1212/WNL.0000000000207777" + }, { "id": "36620207", "doi": "https://doi.org/10.3389/fphys.2022.1089343", @@ -10726,6 +10760,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fphys.2022.1089343; html:https://europepmc.org/articles/PMC9814485; pdf:https://europepmc.org/articles/PMC9814485?pdf=render" }, + { + "id": "34765951", + "doi": "https://doi.org/10.1016/j.eclinm.2021.101163", + "title": "Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.", + "authorString": "Staplin N, Roddick AJ, Emberson J, Reith C, Riding A, Wonnacott A, Kuverji A, Bhandari S, Baigent C, Haynes R, Herrington WG.", + "authorAffiliations": "", + "journalTitle": "EClinicalMedicine", + "pubYear": "2021", + "date": "2021-10-26", + "isOpenAccess": "Y", + "keywords": "Safety; Heart Failure; Randomized Trials; Ckd; Sodium-glucose Co-transporter 2 Inhibitors", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.

Methods

We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468).

Findings

Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes \u223c0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS).

Interpretations

The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date.

Funding

MRC-UK & KRUK.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.eclinm.2021.101163; html:https://europepmc.org/articles/PMC8571171; pdf:https://europepmc.org/articles/PMC8571171?pdf=render" + }, { "id": "34298561", "doi": "https://doi.org/10.1177/2047487320914115", @@ -10744,21 +10795,21 @@ "urls": "doi:https://doi.org/10.1177/2047487320914115" }, { - "id": "34765951", - "doi": "https://doi.org/10.1016/j.eclinm.2021.101163", - "title": "Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.", - "authorString": "Staplin N, Roddick AJ, Emberson J, Reith C, Riding A, Wonnacott A, Kuverji A, Bhandari S, Baigent C, Haynes R, Herrington WG.", + "id": "37578823", + "doi": "https://doi.org/10.2196/45233", + "title": "Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.", + "authorString": "Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.", "authorAffiliations": "", - "journalTitle": "EClinicalMedicine", - "pubYear": "2021", - "date": "2021-10-26", + "journalTitle": "Journal of medical Internet research", + "pubYear": "2023", + "date": "2023-08-14", "isOpenAccess": "Y", - "keywords": "Safety; Heart Failure; Randomized Trials; Ckd; Sodium-glucose Co-transporter 2 Inhibitors", + "keywords": "Depression; Mobile phone; Missing Data; Smartphones; Mobile Health; Wearable Devices; Behavioral Patterns; Digital Phenotypes", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.

Methods

We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468).

Findings

Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes \u223c0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS).

Interpretations

The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date.

Funding

MRC-UK & KRUK.", + "abstract": "

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.eclinm.2021.101163; html:https://europepmc.org/articles/PMC8571171; pdf:https://europepmc.org/articles/PMC8571171?pdf=render" + "urls": "doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088; pdf:https://www.jmir.org/2023/1/e45233/PDF" }, { "id": "37156273", @@ -10862,23 +10913,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render" }, - { - "id": "36715329", - "doi": "https://doi.org/10.1093/bjd/ljac090", - "title": "The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.", - "authorString": "Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.", - "authorAffiliations": "", - "journalTitle": "The British journal of dermatology", - "pubYear": "2023", - "date": "2023-02-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of \u00a3265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.

Objectives

To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.

Methods

The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.

Results

A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to \u00a3119.2-164.4 million.

Conclusions

Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/bjd/ljac090" - }, { "id": "31857590", "doi": "https://doi.org/10.1038/s41597-019-0337-6", @@ -10896,6 +10930,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41597-019-0337-6; html:https://europepmc.org/articles/PMC6923383; pdf:https://europepmc.org/articles/PMC6923383?pdf=render" }, + { + "id": "36715329", + "doi": "https://doi.org/10.1093/bjd/ljac090", + "title": "The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.", + "authorString": "Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "The British journal of dermatology", + "pubYear": "2023", + "date": "2023-02-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of \u00a3265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.

Objectives

To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.

Methods

The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.

Results

A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to \u00a3119.2-164.4 million.

Conclusions

Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/bjd/ljac090" + }, { "id": "34824100", "doi": "https://doi.org/10.1136/openhrt-2021-001769", @@ -10964,23 +11015,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240" }, - { - "id": "37367415", - "doi": "https://doi.org/10.3390/jcdd10060250", - "title": "Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.", - "authorString": "Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.", - "authorAffiliations": "", - "journalTitle": "Journal of cardiovascular development and disease", - "pubYear": "2023", - "date": "2023-06-09", - "isOpenAccess": "Y", - "keywords": "Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF \u2264 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render" - }, { "id": "36606535", "doi": "https://doi.org/10.1111/jdv.18841", @@ -10998,6 +11032,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/jdv.18841" }, + { + "id": "37367415", + "doi": "https://doi.org/10.3390/jcdd10060250", + "title": "Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.", + "authorString": "Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.", + "authorAffiliations": "", + "journalTitle": "Journal of cardiovascular development and disease", + "pubYear": "2023", + "date": "2023-06-09", + "isOpenAccess": "Y", + "keywords": "Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF \u2264 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render" + }, { "id": "31971603", "doi": "https://doi.org/10.2340/00015555-3384", @@ -11304,23 +11355,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fdgth.2021.711941; html:https://europepmc.org/articles/PMC8521945; pdf:https://europepmc.org/articles/PMC8521945?pdf=render" }, - { - "id": "36302124", - "doi": "https://doi.org/10.1080/21645515.2022.2127572", - "title": "Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.", - "authorString": "Ohaeri C, Thomas DR, Salmon J, Cottrell S, Lyons J, Akbari A, Lyons RA, Torabi F, Davies GG, Williams C.", - "authorAffiliations": "", - "journalTitle": "Human vaccines & immunotherapeutics", - "pubYear": "2022", - "date": "2022-10-27", - "isOpenAccess": "Y", - "keywords": "Vaccines; Coronavirus; Cerebral Venous Sinus Thrombosis; Cerebral Venous Thrombosis; Covid19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17\u2009y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28\u2009d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28\u2009d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28\u2009d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?pdf=render; doi:https://doi.org/10.1080/21645515.2022.2127572" - }, { "id": "33845766", "doi": "https://doi.org/10.1186/s12879-021-05992-1", @@ -11338,6 +11372,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12879-021-05992-1; html:https://europepmc.org/articles/PMC8040367; pdf:https://europepmc.org/articles/PMC8040367?pdf=render; pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-021-05992-1" }, + { + "id": "36302124", + "doi": "https://doi.org/10.1080/21645515.2022.2127572", + "title": "Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.", + "authorString": "Ohaeri C, Thomas DR, Salmon J, Cottrell S, Lyons J, Akbari A, Lyons RA, Torabi F, Davies GG, Williams C.", + "authorAffiliations": "", + "journalTitle": "Human vaccines & immunotherapeutics", + "pubYear": "2022", + "date": "2022-10-27", + "isOpenAccess": "Y", + "keywords": "Vaccines; Coronavirus; Cerebral Venous Sinus Thrombosis; Cerebral Venous Thrombosis; Covid19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17\u2009y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28\u2009d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28\u2009d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28\u2009d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?pdf=render; doi:https://doi.org/10.1080/21645515.2022.2127572" + }, { "id": "37609702", "doi": "https://doi.org/10.1002/pds.5681", @@ -11423,23 +11474,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render" }, - { - "id": "36769754", - "doi": "https://doi.org/10.3390/jcm12031106", - "title": "The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.", - "authorString": "Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.", - "authorAffiliations": "", - "journalTitle": "Journal of clinical medicine", - "pubYear": "2023", - "date": "2023-01-31", - "isOpenAccess": "Y", - "keywords": "irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 \u00d7 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 \u00d7 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 \u00d7 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 \u00d7 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render" - }, { "id": "31797917", "doi": "https://doi.org/10.1038/s41398-019-0635-y", @@ -11457,6 +11491,23 @@ "laySummary": "This study assessed for genetic correlation between anhedonia and neuropsychiatric conditions. A polygenic risk score approach was applied to test for association between anhedonia and brain structure and brain function. Findings confirm that using anhedonia as a marker of vulnerability to mental illness. Findings also suggest that genetic risk for state anhedonia influences brain structure", "urls": "doi:https://doi.org/10.1038/s41398-019-0635-y; html:https://europepmc.org/articles/PMC6892870; pdf:https://europepmc.org/articles/PMC6892870?pdf=render" }, + { + "id": "36769754", + "doi": "https://doi.org/10.3390/jcm12031106", + "title": "The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.", + "authorString": "Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.", + "authorAffiliations": "", + "journalTitle": "Journal of clinical medicine", + "pubYear": "2023", + "date": "2023-01-31", + "isOpenAccess": "Y", + "keywords": "irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 \u00d7 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 \u00d7 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 \u00d7 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 \u00d7 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render" + }, { "id": "34514354", "doi": "https://doi.org/10.1093/jamiaopen/ooab001", @@ -11729,6 +11780,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/1471-0528.17531" }, + { + "id": "33521768", + "doi": "https://doi.org/10.1016/s2666-7568(20)30011-8", + "title": "Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.", + "authorString": "Cox LS, Bellantuono I, Lord JM, Sapey E, Mannick JB, Partridge L, Gordon AL, Steves CJ, Witham MD.", + "authorAffiliations": "", + "journalTitle": "The lancet. Healthy longevity", + "pubYear": "2020", + "date": "2020-11-09", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render" + }, { "id": "36564466", "doi": "https://doi.org/10.1038/s41598-022-26141-x", @@ -11763,23 +11831,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1001/jamaneurol.2023.1580" }, - { - "id": "33521768", - "doi": "https://doi.org/10.1016/s2666-7568(20)30011-8", - "title": "Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.", - "authorString": "Cox LS, Bellantuono I, Lord JM, Sapey E, Mannick JB, Partridge L, Gordon AL, Steves CJ, Witham MD.", - "authorAffiliations": "", - "journalTitle": "The lancet. Healthy longevity", - "pubYear": "2020", - "date": "2020-11-09", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render" - }, { "id": "33619467", "doi": "https://doi.org/10.1093/jamiaopen/ooaa047", @@ -11865,23 +11916,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1123/pes.2021-0174" }, - { - "id": "36571960", - "doi": "https://doi.org/10.1016/j.bjps.2022.11.049", - "title": "Artificial intelligence in the management and treatment of burns: A systematic review and meta-analyses.", - "authorString": "Taib BG, Karwath A, Wensley K, Minku L, Gkoutos GV, Moiemen N.", - "authorAffiliations": "", - "journalTitle": "Journal of plastic, reconstructive & aesthetic surgery : JPRAS", - "pubYear": "2023", - "date": "2022-11-23", - "isOpenAccess": "N", - "keywords": "Burns; Systematic review; Machine Learning (Ml); Artificial Intelligence (Ai); Diagnostic Test Meta Analyses", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction and aim

Artificial Intelligence (AI) is already being successfully employed to aid the interpretation of multiple facets of burns care. In the light of the growing influence of AI, this systematic review and diagnostic test accuracy meta-analyses aim to appraise and summarise the current direction of research in this field.

Method

A systematic literature review was conducted of relevant studies published between 1990 and 2021, yielding 35 studies. Twelve studies were suitable for a Diagnostic Test Meta-Analyses.

Results

The studies generally focussed on burn depth (Accuracy 68.9%-95.4%, Sensitivity 90.8% and Specificity 84.4%), burn segmentation (Accuracy 76.0%-99.4%, Sensitivity 97.9% and specificity 97.6%) and burn related mortality (Accuracy >90%-97.5% Sensitivity 92.9% and specificity 93.4%). Neural networks were the most common machine learning (ML) algorithm utilised in 69% of the studies. The QUADAS-2 tool identified significant heterogeneity between studies.

Discussion

The potential application of AI in the management of burns patients is promising, especially given its propitious results across a spectrum of dimensions, including burn depth, size, mortality, related sepsis and acute kidney injuries. The accuracy of the results analysed within this study is comparable to current practices in burns care.

Conclusion

The application of AI in the treatment and management of burns patients, as a series of point of care diagnostic adjuncts, is promising. Whilst AI is a potentially valuable tool, a full evaluation of its current utility and potential is limited by significant variations in research methodology and reporting.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.bjps.2022.11.049" - }, { "id": "34161326", "doi": "https://doi.org/10.1371/journal.pcbi.1009121", @@ -11899,6 +11933,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render" }, + { + "id": "36571960", + "doi": "https://doi.org/10.1016/j.bjps.2022.11.049", + "title": "Artificial intelligence in the management and treatment of burns: A systematic review and meta-analyses.", + "authorString": "Taib BG, Karwath A, Wensley K, Minku L, Gkoutos GV, Moiemen N.", + "authorAffiliations": "", + "journalTitle": "Journal of plastic, reconstructive & aesthetic surgery : JPRAS", + "pubYear": "2023", + "date": "2022-11-23", + "isOpenAccess": "N", + "keywords": "Burns; Systematic review; Machine Learning (Ml); Artificial Intelligence (Ai); Diagnostic Test Meta Analyses", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction and aim

Artificial Intelligence (AI) is already being successfully employed to aid the interpretation of multiple facets of burns care. In the light of the growing influence of AI, this systematic review and diagnostic test accuracy meta-analyses aim to appraise and summarise the current direction of research in this field.

Method

A systematic literature review was conducted of relevant studies published between 1990 and 2021, yielding 35 studies. Twelve studies were suitable for a Diagnostic Test Meta-Analyses.

Results

The studies generally focussed on burn depth (Accuracy 68.9%-95.4%, Sensitivity 90.8% and Specificity 84.4%), burn segmentation (Accuracy 76.0%-99.4%, Sensitivity 97.9% and specificity 97.6%) and burn related mortality (Accuracy >90%-97.5% Sensitivity 92.9% and specificity 93.4%). Neural networks were the most common machine learning (ML) algorithm utilised in 69% of the studies. The QUADAS-2 tool identified significant heterogeneity between studies.

Discussion

The potential application of AI in the management of burns patients is promising, especially given its propitious results across a spectrum of dimensions, including burn depth, size, mortality, related sepsis and acute kidney injuries. The accuracy of the results analysed within this study is comparable to current practices in burns care.

Conclusion

The application of AI in the treatment and management of burns patients, as a series of point of care diagnostic adjuncts, is promising. Whilst AI is a potentially valuable tool, a full evaluation of its current utility and potential is limited by significant variations in research methodology and reporting.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.bjps.2022.11.049" + }, { "id": "36446449", "doi": "https://doi.org/10.1136/bmjopen-2022-061849", @@ -12001,6 +12052,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render" }, + { + "id": "29938349", + "doi": "https://doi.org/10.1007/s11892-018-1021-5", + "title": "Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment.", + "authorString": "Strawbridge RJ, van Zuydam NR.", + "authorAffiliations": "", + "journalTitle": "Current diabetes reports", + "pubYear": "2018", + "date": "2018-06-25", + "isOpenAccess": "Y", + "keywords": "Type 2 diabetes; Ischemic stroke; coronary artery disease; risk factors; Peripheral Artery Disease; Genetics; Mendelian Randomisation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose of review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render" + }, { "id": "35896970", "doi": "https://doi.org/10.1186/s12879-022-07628-4", @@ -12035,23 +12103,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/17407745211069985; html:https://europepmc.org/articles/PMC9036147; pdf:https://europepmc.org/articles/PMC9036147?pdf=render" }, - { - "id": "29938349", - "doi": "https://doi.org/10.1007/s11892-018-1021-5", - "title": "Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment.", - "authorString": "Strawbridge RJ, van Zuydam NR.", - "authorAffiliations": "", - "journalTitle": "Current diabetes reports", - "pubYear": "2018", - "date": "2018-06-25", - "isOpenAccess": "Y", - "keywords": "Type 2 diabetes; Ischemic stroke; coronary artery disease; risk factors; Peripheral Artery Disease; Genetics; Mendelian Randomisation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose of review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render" - }, { "id": "32310142", "doi": "https://doi.org/10.2196/14306", @@ -12154,23 +12205,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/bs.acc.2020.08.002" }, - { - "id": "33413610", - "doi": "https://doi.org/10.1186/s13073-020-00822-6", - "title": "An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.", - "authorString": "Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.", - "authorAffiliations": "", - "journalTitle": "Genome medicine", - "pubYear": "2021", - "date": "2021-01-07", - "isOpenAccess": "Y", - "keywords": "Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online \"immuno-analytics\" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (>\u200986%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render" - }, { "id": "34158612", "doi": "https://doi.org/10.1038/s41366-021-00846-x", @@ -12188,6 +12222,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41366-021-00846-x; html:https://europepmc.org/articles/PMC8310793; pdf:https://europepmc.org/articles/PMC8310793?pdf=render" }, + { + "id": "33413610", + "doi": "https://doi.org/10.1186/s13073-020-00822-6", + "title": "An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.", + "authorString": "Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.", + "authorAffiliations": "", + "journalTitle": "Genome medicine", + "pubYear": "2021", + "date": "2021-01-07", + "isOpenAccess": "Y", + "keywords": "Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online \"immuno-analytics\" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (>\u200986%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render" + }, { "id": "34266851", "doi": "https://doi.org/10.1136/bmjhci-2021-100356", @@ -12205,6 +12256,40 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render" }, + { + "id": "30423068", + "doi": "https://doi.org/10.1093/bioinformatics/bty605", + "title": "Ontology-based validation and identification of regulatory phenotypes.", + "authorString": "Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.", + "authorAffiliations": "", + "journalTitle": "Bioinformatics (Oxford, England)", + "pubYear": "2018", + "date": "2018-09-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "Applied Analytics, The Human Phenome", + "healthCategories": "", + "abstract": "

Motivation

Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.

Results

We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.

Availability and implementation

https://github.com/bio-ontology-research-group/phenogocon.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render; pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf" + }, + { + "id": "33710281", + "doi": "https://doi.org/10.1093/ageing/afab060", + "title": "COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).", + "authorString": "Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hayward A, Shallcross L.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2021", + "date": "2021-06-01", + "isOpenAccess": "Y", + "keywords": "Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

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

Results

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

Conclusions

findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render" + }, { "id": "35277405", "doi": "https://doi.org/10.1136/bmjopen-2021-055070", @@ -12239,40 +12324,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render" }, - { - "id": "33710281", - "doi": "https://doi.org/10.1093/ageing/afab060", - "title": "COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).", - "authorString": "Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hayward A, Shallcross L.", - "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2021", - "date": "2021-06-01", - "isOpenAccess": "Y", - "keywords": "Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods

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

Results

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

Conclusions

findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render" - }, - { - "id": "30423068", - "doi": "https://doi.org/10.1093/bioinformatics/bty605", - "title": "Ontology-based validation and identification of regulatory phenotypes.", - "authorString": "Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.", - "authorAffiliations": "", - "journalTitle": "Bioinformatics (Oxford, England)", - "pubYear": "2018", - "date": "2018-09-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Applied Analytics, The Human Phenome", - "healthCategories": "", - "abstract": "

Motivation

Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.

Results

We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.

Availability and implementation

https://github.com/bio-ontology-research-group/phenogocon.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render; pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf" - }, { "id": "31616478", "doi": "https://doi.org/10.3389/fgene.2019.00922", @@ -12630,23 +12681,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render" }, - { - "id": "35296643", - "doi": "https://doi.org/10.1038/s41467-022-28517-z", - "title": "Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.", - "authorString": "Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2022", - "date": "2022-03-16", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Anti tumour necrosis factor (anti-TNF)\u00a0drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7\u2009U/mL [6.2] vs 4555.3\u2009U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7\u2009U/mL [5.0] vs 784.0\u2009U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render; pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf" - }, { "id": "35898465", "doi": "https://doi.org/10.3389/fendo.2022.888924", @@ -12664,6 +12698,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render" }, + { + "id": "35296643", + "doi": "https://doi.org/10.1038/s41467-022-28517-z", + "title": "Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.", + "authorString": "Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2022", + "date": "2022-03-16", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Anti tumour necrosis factor (anti-TNF)\u00a0drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7\u2009U/mL [6.2] vs 4555.3\u2009U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7\u2009U/mL [5.0] vs 784.0\u2009U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render; pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf" + }, { "id": "35765786", "doi": "https://doi.org/10.7189/jogh.12.04052", @@ -12953,23 +13004,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/mnfr.202100316; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mnfr.202100316" }, - { - "id": "37489768", - "doi": "https://doi.org/10.1161/jaha.122.029296", - "title": "Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.", - "authorString": "Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2023", - "date": "2023-07-25", - "isOpenAccess": "Y", - "keywords": "Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108\u2009685 participants aged 40 to 69\u2009years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296" - }, { "id": "33280008", "doi": "https://doi.org/10.1093/cercor/bhaa345", @@ -12987,6 +13021,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render" }, + { + "id": "37489768", + "doi": "https://doi.org/10.1161/jaha.122.029296", + "title": "Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.", + "authorString": "Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2023", + "date": "2023-07-25", + "isOpenAccess": "Y", + "keywords": "Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108\u2009685 participants aged 40 to 69\u2009years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296" + }, { "id": "35640889", "doi": "https://doi.org/10.1093/ehjci/jeac101", @@ -13277,21 +13328,21 @@ "urls": "doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268" }, { - "id": "37606853", - "doi": "https://doi.org/10.1007/s00520-023-07944-8", - "title": "The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.", - "authorString": "Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.", + "id": "32616677", + "doi": "https://doi.org/10.1212/wnl.0000000000009924", + "title": "Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.", + "authorString": "Rannikm\u00e4e K, Ngoh K, Bush K, Al-Shahi Salman R, Doubal F, Flaig R, Henshall DE, Hutchison A, Nolan J, Osborne S, Samarasekera N, Schnier C, Whiteley W, Wilkinson T, Wilson K, Woodfield R, Zhang Q, Allen N, Sudlow CLM.", "authorAffiliations": "", - "journalTitle": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer", - "pubYear": "2023", - "date": "2023-08-22", + "journalTitle": "Neurology", + "pubYear": "2020", + "date": "2020-07-02", "isOpenAccess": "Y", - "keywords": "Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Purpose

Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods

A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Results

We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.

Conclusions

We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.", + "abstract": "

Objective

In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes.

Methods

In a regional UKB subpopulation (n = 17,249), we identified all participants with \u22651 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type.

Results

Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise.

Conclusions

Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.", "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf" + "urls": "doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render" }, { "id": "35870544", @@ -13311,21 +13362,21 @@ "urls": "doi:https://doi.org/10.1016/j.cpcardiol.2022.101330" }, { - "id": "32616677", - "doi": "https://doi.org/10.1212/wnl.0000000000009924", - "title": "Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.", - "authorString": "Rannikm\u00e4e K, Ngoh K, Bush K, Al-Shahi Salman R, Doubal F, Flaig R, Henshall DE, Hutchison A, Nolan J, Osborne S, Samarasekera N, Schnier C, Whiteley W, Wilkinson T, Wilson K, Woodfield R, Zhang Q, Allen N, Sudlow CLM.", + "id": "37606853", + "doi": "https://doi.org/10.1007/s00520-023-07944-8", + "title": "The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.", + "authorString": "Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.", "authorAffiliations": "", - "journalTitle": "Neurology", - "pubYear": "2020", - "date": "2020-07-02", + "journalTitle": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer", + "pubYear": "2023", + "date": "2023-08-22", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes.

Methods

In a regional UKB subpopulation (n = 17,249), we identified all participants with \u22651 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type.

Results

Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise.

Conclusions

Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.", + "abstract": "

Purpose

Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods

A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Results

We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.

Conclusions

We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.", "laySummary": "", - "urls": "doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render" + "urls": "doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf" }, { "id": "32926504", @@ -13378,6 +13429,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688" }, + { + "id": "32460529", + "doi": "https://doi.org/10.1161/circimaging.119.010389", + "title": "Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.", + "authorString": "Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.", + "authorAffiliations": "", + "journalTitle": "Circulation. Cardiovascular imaging", + "pubYear": "2020", + "date": "2020-05-28", + "isOpenAccess": "N", + "keywords": "Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389" + }, { "id": "36864090", "doi": "https://doi.org/10.1038/s41598-023-30369-6", @@ -13412,23 +13480,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1183/23120541.00591-2022; html:https://europepmc.org/articles/PMC10152257; pdf:https://europepmc.org/articles/PMC10152257?pdf=render" }, - { - "id": "32460529", - "doi": "https://doi.org/10.1161/circimaging.119.010389", - "title": "Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.", - "authorString": "Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.", - "authorAffiliations": "", - "journalTitle": "Circulation. Cardiovascular imaging", - "pubYear": "2020", - "date": "2020-05-28", - "isOpenAccess": "N", - "keywords": "Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389" - }, { "id": "33147524", "doi": "https://doi.org/10.1016/j.puhe.2020.08.027", @@ -13463,23 +13514,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render; pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf" }, - { - "id": "36197964", - "doi": "https://doi.org/10.1126/scitranslmed.abq4810", - "title": "Comment on \"A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk\".", - "authorString": "Kivim\u00e4ki M, Hingorani AD, Lindbohm JV.", - "authorAffiliations": "", - "journalTitle": "Science translational medicine", - "pubYear": "2022", - "date": "2022-10-05", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A 27-protein signature has been proposed to predict cardiovascular disease, but its applicability in clinical decision-making remains unclear.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1126/scitranslmed.abq4810" - }, { "id": "30240446", "doi": "https://doi.org/10.1371/journal.pone.0203896", @@ -13498,21 +13532,21 @@ "urls": "doi:https://doi.org/10.1371/journal.pone.0203896; html:https://europepmc.org/articles/PMC6150505; pdf:https://europepmc.org/articles/PMC6150505?pdf=render" }, { - "id": "37505992", - "doi": "https://doi.org/10.1093/ageing/afad136", - "title": "The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.", - "authorString": "Cheong VL, Mehdizadeh D, Todd OM, Gardner P, Zaman H, Clegg A, Alldred DP, Faisal M.", + "id": "36197964", + "doi": "https://doi.org/10.1126/scitranslmed.abq4810", + "title": "Comment on \"A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk\".", + "authorString": "Kivim\u00e4ki M, Hingorani AD, Lindbohm JV.", "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "Y", - "keywords": "Frailty; Older People; Older Adults; Routine Data; Anticholinergic Burden; Structured Medication Review", + "journalTitle": "Science translational medicine", + "pubYear": "2022", + "date": "2022-10-05", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status.

Methods

Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged \u226565 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum).

Results

In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)).

Conclusions

Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.", + "abstract": "A 27-protein signature has been proposed to predict cardiovascular disease, but its applicability in clinical decision-making remains unclear.", "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf" + "urls": "doi:https://doi.org/10.1126/scitranslmed.abq4810" }, { "id": "32788201", @@ -13531,6 +13565,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render" }, + { + "id": "37505992", + "doi": "https://doi.org/10.1093/ageing/afad136", + "title": "The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.", + "authorString": "Cheong VL, Mehdizadeh D, Todd OM, Gardner P, Zaman H, Clegg A, Alldred DP, Faisal M.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2023", + "date": "2023-07-01", + "isOpenAccess": "Y", + "keywords": "Frailty; Older People; Older Adults; Routine Data; Anticholinergic Burden; Structured Medication Review", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status.

Methods

Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged \u226565 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum).

Results

In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)).

Conclusions

Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render; pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf" + }, { "id": "37456658", "doi": "https://doi.org/10.12688/hrbopenres.13667.1", @@ -13769,23 +13820,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render" }, - { - "id": "36050271", - "doi": "https://doi.org/10.1016/s2589-7500(22)00151-0", - "title": "CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.", - "authorString": "Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, L\u00f8gstrup S, Lumbers RT, L\u00fcscher TF, McGreavy P, Pi\u00f1a IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2022", - "date": "2022-08-29", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00151-0; doi:https://doi.org/10.1016/s2589-7500(22)00151-0" - }, { "id": "34564897", "doi": "https://doi.org/10.1002/gps.5627", @@ -13803,6 +13837,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/gps.5627; html:https://europepmc.org/articles/PMC9292841; pdf:https://europepmc.org/articles/PMC9292841?pdf=render" }, + { + "id": "36050271", + "doi": "https://doi.org/10.1016/s2589-7500(22)00151-0", + "title": "CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.", + "authorString": "Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, L\u00f8gstrup S, Lumbers RT, L\u00fcscher TF, McGreavy P, Pi\u00f1a IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2022", + "date": "2022-08-29", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00151-0; doi:https://doi.org/10.1016/s2589-7500(22)00151-0" + }, { "id": "37440761", "doi": "https://doi.org/10.1093/ehjci/jead166", @@ -13905,23 +13956,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1098/rstb.2018.0276; html:https://europepmc.org/articles/PMC6558557; pdf:https://europepmc.org/articles/PMC6558557?pdf=render; pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2018.0276" }, - { - "id": "37337639", - "doi": "https://doi.org/10.1002/ctm2.1291", - "title": "Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.", - "authorString": "Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.", - "authorAffiliations": "", - "journalTitle": "Clinical and translational medicine", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "Y", - "keywords": "Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.

Methods

The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.

Results

We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.

Conclusions

Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render" - }, { "id": "33516523", "doi": "https://doi.org/10.1016/j.jaci.2020.12.001", @@ -13939,6 +13973,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render" }, + { + "id": "37337639", + "doi": "https://doi.org/10.1002/ctm2.1291", + "title": "Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.", + "authorString": "Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.", + "authorAffiliations": "", + "journalTitle": "Clinical and translational medicine", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "Y", + "keywords": "Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.

Methods

The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.

Results

We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.

Conclusions

Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render" + }, { "id": "31685485", "doi": "https://doi.org/10.1136/bmjopen-2019-031365", @@ -14007,23 +14058,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render" }, - { - "id": "36580444", - "doi": "https://doi.org/10.1371/journal.pmed.1004141", - "title": "Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.", - "authorString": "Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2022", - "date": "2022-12-29", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

Methods and findings

The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

Conclusions

Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render" - }, { "id": "31611193", "doi": "https://doi.org/10.1136/archdischild-2019-317248", @@ -14041,6 +14075,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/archdischild-2019-317248; html:https://europepmc.org/articles/PMC7146921; pdf:https://europepmc.org/articles/PMC7146921?pdf=render" }, + { + "id": "36580444", + "doi": "https://doi.org/10.1371/journal.pmed.1004141", + "title": "Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.", + "authorString": "Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2022", + "date": "2022-12-29", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

Methods and findings

The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

Conclusions

Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render" + }, { "id": "34169636", "doi": "https://doi.org/10.1002/pst.2148", @@ -14075,23 +14126,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333" }, - { - "id": "34286192", - "doi": "https://doi.org/10.7861/fhj.2021-0083", - "title": "Making trials part of good clinical care: lessons from the RECOVERY trial.", - "authorString": "Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.", - "authorAffiliations": "", - "journalTitle": "Future healthcare journal", - "pubYear": "2021", - "date": "2021-07-01", - "isOpenAccess": "N", - "keywords": "Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.", - "laySummary": "", - "urls": "doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083" - }, { "id": "34399584", "doi": "https://doi.org/10.1161/strokeaha.120.032619", @@ -14109,6 +14143,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619" }, + { + "id": "34286192", + "doi": "https://doi.org/10.7861/fhj.2021-0083", + "title": "Making trials part of good clinical care: lessons from the RECOVERY trial.", + "authorString": "Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.", + "authorAffiliations": "", + "journalTitle": "Future healthcare journal", + "pubYear": "2021", + "date": "2021-07-01", + "isOpenAccess": "N", + "keywords": "Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.", + "laySummary": "", + "urls": "doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083" + }, { "id": "34890511", "doi": "https://doi.org/10.1080/09638288.2021.1992517", @@ -14177,23 +14228,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render" }, - { - "id": "37067859", - "doi": "https://doi.org/10.1136/bmjmed-2022-000245", - "title": "Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.", - "authorString": "Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .", - "authorAffiliations": "", - "journalTitle": "BMJ medicine", - "pubYear": "2023", - "date": "2023-02-14", - "isOpenAccess": "Y", - "keywords": "epidemiology; Heart Failure; Cardiology; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.

Design

Registry based observational study.

Setting

74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.

Participants

All adults (aged \u226518 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11\u2009167 patients).

Main outcome measures

Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with \u226520 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.

Results

Of 11\u2009167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).

Conclusions

In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render" - }, { "id": "31153319", "doi": "https://doi.org/10.1121/1.5100272", @@ -14211,6 +14245,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1121/1.5100272; html:https://europepmc.org/articles/PMC6509044; pdf:https://europepmc.org/articles/PMC6509044?pdf=render; doi:https://doi.org/10.1121/1.5100272" }, + { + "id": "37067859", + "doi": "https://doi.org/10.1136/bmjmed-2022-000245", + "title": "Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.", + "authorString": "Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .", + "authorAffiliations": "", + "journalTitle": "BMJ medicine", + "pubYear": "2023", + "date": "2023-02-14", + "isOpenAccess": "Y", + "keywords": "epidemiology; Heart Failure; Cardiology; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.

Design

Registry based observational study.

Setting

74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.

Participants

All adults (aged \u226518 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11\u2009167 patients).

Main outcome measures

Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with \u226520 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.

Results

Of 11\u2009167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).

Conclusions

In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render" + }, { "id": "33653161", "doi": "https://doi.org/10.1177/1740774520976617", @@ -14568,23 +14619,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render" }, - { - "id": "37303488", - "doi": "https://doi.org/10.1136/bmjmed-2022-000392", - "title": "Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.", - "authorString": "Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.", - "authorAffiliations": "", - "journalTitle": "BMJ medicine", - "pubYear": "2023", - "date": "2023-05-11", - "isOpenAccess": "Y", - "keywords": "Primary Health Care; Medical Informatics; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age \u226565 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age \u226565 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render" - }, { "id": "34985035", "doi": "https://doi.org/10.1097/htr.0000000000000741", @@ -14603,21 +14637,21 @@ "urls": "doi:https://doi.org/10.1097/HTR.0000000000000741" }, { - "id": "32954362", - "doi": "https://doi.org/10.1038/s43016-020-0093-y", - "title": "Nutriome-metabolome relationships provide insights into dietary intake and metabolism.", - "authorString": "Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.", + "id": "37303488", + "doi": "https://doi.org/10.1136/bmjmed-2022-000392", + "title": "Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.", + "authorString": "Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.", "authorAffiliations": "", - "journalTitle": "Nature food", - "pubYear": "2020", - "date": "2020-06-22", - "isOpenAccess": "N", - "keywords": "", + "journalTitle": "BMJ medicine", + "pubYear": "2023", + "date": "2023-05-11", + "isOpenAccess": "Y", + "keywords": "Primary Health Care; Medical Informatics; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.", + "abstract": "

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age \u226565 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age \u226565 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y" + "urls": "doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render" }, { "id": "34847088", @@ -14653,6 +14687,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041980; html:https://europepmc.org/articles/PMC6749969; pdf:https://europepmc.org/articles/PMC6749969?pdf=render; doi:https://doi.org/10.1161/circulationaha.119.041980" }, + { + "id": "32954362", + "doi": "https://doi.org/10.1038/s43016-020-0093-y", + "title": "Nutriome-metabolome relationships provide insights into dietary intake and metabolism.", + "authorString": "Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.", + "authorAffiliations": "", + "journalTitle": "Nature food", + "pubYear": "2020", + "date": "2020-06-22", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y" + }, { "id": "37074763", "doi": "https://doi.org/10.2196/44237", @@ -14721,23 +14772,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render" }, - { - "id": "37119604", - "doi": "https://doi.org/10.1016/j.canep.2023.102367", - "title": "Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.", - "authorString": "Greene GJ, Thomson CS, Donnelly D, Chung D, Bhatti L, Gavin AT, Lawler M, Huws DW, Rolles MJ, Benn\u00e9e F, Morrison DS.", - "authorAffiliations": "", - "journalTitle": "Cancer epidemiology", - "pubYear": "2023", - "date": "2023-04-21", - "isOpenAccess": "Y", - "keywords": "Pandemic; Population-based Incidence; Covid-19; Sars-cov-2; Pathology-Confirmed Cancer", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI).

Methods

Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR).

Results

Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20).

Conclusion

PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.canep.2023.102367; html:https://europepmc.org/articles/PMC10121133; pdf:https://europepmc.org/articles/PMC10121133?pdf=render" - }, { "id": "34671274", "doi": "https://doi.org/10.3389/fphys.2021.730736", @@ -14755,6 +14789,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render" }, + { + "id": "37119604", + "doi": "https://doi.org/10.1016/j.canep.2023.102367", + "title": "Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.", + "authorString": "Greene GJ, Thomson CS, Donnelly D, Chung D, Bhatti L, Gavin AT, Lawler M, Huws DW, Rolles MJ, Benn\u00e9e F, Morrison DS.", + "authorAffiliations": "", + "journalTitle": "Cancer epidemiology", + "pubYear": "2023", + "date": "2023-04-21", + "isOpenAccess": "Y", + "keywords": "Pandemic; Population-based Incidence; Covid-19; Sars-cov-2; Pathology-Confirmed Cancer", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI).

Methods

Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR).

Results

Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20).

Conclusion

PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.canep.2023.102367; html:https://europepmc.org/articles/PMC10121133; pdf:https://europepmc.org/articles/PMC10121133?pdf=render" + }, { "id": "36942567", "doi": "https://doi.org/10.1161/circep.122.011585", @@ -14925,6 +14976,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render; pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf" }, + { + "id": "32763878", + "doi": "https://doi.org/10.2196/18690", + "title": "Notifications to Improve Engagement With an Alcohol Reduction App: Protocol for a Micro-Randomized Trial.", + "authorString": "Bell L, Garnett C, Qian T, Perski O, Potts HWW, Williamson E.", + "authorAffiliations": "", + "journalTitle": "JMIR research protocols", + "pubYear": "2020", + "date": "2020-08-07", + "isOpenAccess": "Y", + "keywords": "Alcohol; Engagement; Mhealth; Mobile Health; Excessive Alcohol Consumption; Smartphone App; Push Notifications; Digital Behavior Change; Micro-randomized Trial", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Drink Less is a behavior change app that aims to help users in the general adult population reduce hazardous and harmful alcohol consumption. The app includes a daily push notification, delivered at 11 am, asking users to \"Please complete your mood and drinking diaries.\" Previous analysis of Drink Less engagement data suggests the current notification strongly influences how users engage with the app in the subsequent hour. To exploit a potential increase of vulnerability of excess drinking and opportunity to engage with the app in the evenings, we changed the delivery time from 11 am to 8 pm. We now aim to further optimise the content and sequence of notifications, testing 30 new evidence-informed notifications targeting the user's perceived usefulness of the app.

Objective

The primary objective is to assess whether sending a notification at 8 pm increases behavioral engagement (opening the app) in the subsequent hour. Secondary objectives include comparing the effect of the new bank of messages with the standard message and effect moderation over time. We also aim to more generally understand the role notifications have on the overall duration, depth, and frequency of engagement with Drink Less over the first 30 days after download.

Methods

This is a protocol for a micro-randomized trial with two additional parallel arms. Inclusion criteria are Drink Less users who (1) consent to participate in the trial; (2) self-report a baseline Alcohol Use Disorders Identification Test score of 8 or above; (3) reside in the United Kingdom; (4) age \u226518 years and; (5) report interest in drinking less alcohol. In the micro-randomized trial, participants will be randomized daily at 8 pm to receive no notification, a notification with text from the new message bank, or the standard message. The primary outcome is the time-varying, binary outcome of \"Did the user open the app in the hour from 8 pm to 9 pm?\". The primary analysis will estimate the marginal relative risk for the notifications using an estimator developed for micro-randomized trials with binary outcomes. Participants randomized to the parallel arms will receive no notifications (Secondary Arm A), or the standard notification delivered daily at 11 am (Secondary Arm B) over 30 days, allowing the comparison of overall engagement between different notification delivery strategies.

Results

Approval was granted by the University College of London's Departmental Research Ethics Committee (CEHP/2016/556) on October 11, 2019, and The London School of Hygiene and Tropical Medicine Interventions Research Ethics Committee (17929) on November 27, 2019. Recruitment began on January 2, 2020, and is ongoing.

Conclusions

Understanding how push notifications may impact engagement with a behavior change app can lead to further improvements in engagement, and ultimately help users reduce their alcohol consumption. This understanding may also be generalizable to other apps that target a variety of behavior changes.

International registered report identifier (irrid)

DERR1-10.2196/18690.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945" + }, { "id": "37394283", "doi": "https://doi.org/10.1002/ehf2.14444", @@ -14943,21 +15011,21 @@ "urls": "doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444" }, { - "id": "32763878", - "doi": "https://doi.org/10.2196/18690", - "title": "Notifications to Improve Engagement With an Alcohol Reduction App: Protocol for a Micro-Randomized Trial.", - "authorString": "Bell L, Garnett C, Qian T, Perski O, Potts HWW, Williamson E.", + "id": "36543768", + "doi": "https://doi.org/10.1038/s41467-022-35321-2", + "title": "Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants.", + "authorString": "McCracken C, Raisi-Estabragh Z, Veldsman M, Raman B, Dennis A, Husain M, Nichols TE, Petersen SE, Neubauer S.", "authorAffiliations": "", - "journalTitle": "JMIR research protocols", - "pubYear": "2020", - "date": "2020-08-07", + "journalTitle": "Nature communications", + "pubYear": "2022", + "date": "2022-12-21", "isOpenAccess": "Y", - "keywords": "Alcohol; Engagement; Mhealth; Mobile Health; Excessive Alcohol Consumption; Smartphone App; Push Notifications; Digital Behavior Change; Micro-randomized Trial", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Drink Less is a behavior change app that aims to help users in the general adult population reduce hazardous and harmful alcohol consumption. The app includes a daily push notification, delivered at 11 am, asking users to \"Please complete your mood and drinking diaries.\" Previous analysis of Drink Less engagement data suggests the current notification strongly influences how users engage with the app in the subsequent hour. To exploit a potential increase of vulnerability of excess drinking and opportunity to engage with the app in the evenings, we changed the delivery time from 11 am to 8 pm. We now aim to further optimise the content and sequence of notifications, testing 30 new evidence-informed notifications targeting the user's perceived usefulness of the app.

Objective

The primary objective is to assess whether sending a notification at 8 pm increases behavioral engagement (opening the app) in the subsequent hour. Secondary objectives include comparing the effect of the new bank of messages with the standard message and effect moderation over time. We also aim to more generally understand the role notifications have on the overall duration, depth, and frequency of engagement with Drink Less over the first 30 days after download.

Methods

This is a protocol for a micro-randomized trial with two additional parallel arms. Inclusion criteria are Drink Less users who (1) consent to participate in the trial; (2) self-report a baseline Alcohol Use Disorders Identification Test score of 8 or above; (3) reside in the United Kingdom; (4) age \u226518 years and; (5) report interest in drinking less alcohol. In the micro-randomized trial, participants will be randomized daily at 8 pm to receive no notification, a notification with text from the new message bank, or the standard message. The primary outcome is the time-varying, binary outcome of \"Did the user open the app in the hour from 8 pm to 9 pm?\". The primary analysis will estimate the marginal relative risk for the notifications using an estimator developed for micro-randomized trials with binary outcomes. Participants randomized to the parallel arms will receive no notifications (Secondary Arm A), or the standard notification delivered daily at 11 am (Secondary Arm B) over 30 days, allowing the comparison of overall engagement between different notification delivery strategies.

Results

Approval was granted by the University College of London's Departmental Research Ethics Committee (CEHP/2016/556) on October 11, 2019, and The London School of Hygiene and Tropical Medicine Interventions Research Ethics Committee (17929) on November 27, 2019. Recruitment began on January 2, 2020, and is ongoing.

Conclusions

Understanding how push notifications may impact engagement with a behavior change app can lead to further improvements in engagement, and ultimately help users reduce their alcohol consumption. This understanding may also be generalizable to other apps that target a variety of behavior changes.

International registered report identifier (irrid)

DERR1-10.2196/18690.", + "abstract": "Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.", "laySummary": "", - "urls": "doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945" + "urls": "doi:https://doi.org/10.1038/s41467-022-35321-2; html:https://europepmc.org/articles/PMC9772225; pdf:https://europepmc.org/articles/PMC9772225?pdf=render; pdf:https://www.nature.com/articles/s41467-022-35321-2.pdf" }, { "id": "37225263", @@ -14977,21 +15045,21 @@ "urls": "doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render" }, { - "id": "36543768", - "doi": "https://doi.org/10.1038/s41467-022-35321-2", - "title": "Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants.", - "authorString": "McCracken C, Raisi-Estabragh Z, Veldsman M, Raman B, Dennis A, Husain M, Nichols TE, Petersen SE, Neubauer S.", + "id": "33503030", + "doi": "https://doi.org/10.1371/journal.pone.0245636", + "title": "Classification of road traffic injury collision characteristics using text mining analysis: Implications for road injury prevention.", + "authorString": "Giummarra MJ, Beck B, Gabbe BJ.", "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2022", - "date": "2022-12-21", + "journalTitle": "PloS one", + "pubYear": "2021", + "date": "2021-01-27", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.", + "abstract": "Road traffic injuries are a leading cause of morbidity and mortality globally. Understanding circumstances leading to road traffic injury is crucial to improve road safety, and implement countermeasures to reduce the incidence and severity of road trauma. We aimed to characterise crash characteristics of road traffic collisions in Victoria, Australia, and to examine the relationship between crash characteristics and fault attribution. Data were extracted from the Victorian State Trauma Registry for motor vehicle drivers, motorcyclists, pedal cyclists and pedestrians with a no-fault compensation claim, aged > = 16 years and injured 2010-2016. People with intentional injury, serious head injury, no compensation claim/missing injury event description or who died < = 12-months post-injury were excluded, resulting in a sample of 2,486. Text mining of the injury event using QDA Miner and Wordstat was used to classify crash circumstances for each road user group. Crashes in which no other was at fault included circumstances involving lost control or avoiding a hazard, mechanical failure or medical conditions. Collisions in which another was predominantly at fault occurred at intersections with another vehicle entering from an adjacent direction, and head-on collisions. Crashes with higher prevalence of unknown fault included multi-vehicle collisions, pedal cyclists injured in rear-end collisions, and pedestrians hit while crossing the road or navigating slow traffic areas. We discuss several methods to promote road safety and to reduce the incidence and severity of road traffic injuries. Our recommendations take into consideration the incidence and impact of road trauma for different types of road users, and include engineering and infrastructure controls through to interventions targeting or accommodating human behaviour.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-022-35321-2; html:https://europepmc.org/articles/PMC9772225; pdf:https://europepmc.org/articles/PMC9772225?pdf=render; pdf:https://www.nature.com/articles/s41467-022-35321-2.pdf" + "urls": "doi:https://doi.org/10.1371/journal.pone.0245636; html:https://europepmc.org/articles/PMC7840051; pdf:https://europepmc.org/articles/PMC7840051?pdf=render" }, { "id": "34427560", @@ -15010,23 +15078,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1684/ejd.2021.4108" }, - { - "id": "33503030", - "doi": "https://doi.org/10.1371/journal.pone.0245636", - "title": "Classification of road traffic injury collision characteristics using text mining analysis: Implications for road injury prevention.", - "authorString": "Giummarra MJ, Beck B, Gabbe BJ.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2021", - "date": "2021-01-27", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Road traffic injuries are a leading cause of morbidity and mortality globally. Understanding circumstances leading to road traffic injury is crucial to improve road safety, and implement countermeasures to reduce the incidence and severity of road trauma. We aimed to characterise crash characteristics of road traffic collisions in Victoria, Australia, and to examine the relationship between crash characteristics and fault attribution. Data were extracted from the Victorian State Trauma Registry for motor vehicle drivers, motorcyclists, pedal cyclists and pedestrians with a no-fault compensation claim, aged > = 16 years and injured 2010-2016. People with intentional injury, serious head injury, no compensation claim/missing injury event description or who died < = 12-months post-injury were excluded, resulting in a sample of 2,486. Text mining of the injury event using QDA Miner and Wordstat was used to classify crash circumstances for each road user group. Crashes in which no other was at fault included circumstances involving lost control or avoiding a hazard, mechanical failure or medical conditions. Collisions in which another was predominantly at fault occurred at intersections with another vehicle entering from an adjacent direction, and head-on collisions. Crashes with higher prevalence of unknown fault included multi-vehicle collisions, pedal cyclists injured in rear-end collisions, and pedestrians hit while crossing the road or navigating slow traffic areas. We discuss several methods to promote road safety and to reduce the incidence and severity of road traffic injuries. Our recommendations take into consideration the incidence and impact of road trauma for different types of road users, and include engineering and infrastructure controls through to interventions targeting or accommodating human behaviour.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0245636; html:https://europepmc.org/articles/PMC7840051; pdf:https://europepmc.org/articles/PMC7840051?pdf=render" - }, { "id": "35673545", "doi": "https://doi.org/10.12688/wellcomeopenres.17231.2", @@ -15061,23 +15112,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1080/02640414.2021.1928409" }, - { - "id": "37223892", - "doi": "https://doi.org/10.1111/dme.15153", - "title": "Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.", - "authorString": "Phillips K, Hazlehurst JM, Sheppard C, Bellary S, Hanif W, Karamat MA, Crowe FL, Stone A, Thomas GN, Peracha J, Fenton A, Sainsbury C, Nirantharakumar K, Dasgupta I.", - "authorAffiliations": "", - "journalTitle": "Diabetic medicine : a journal of the British Diabetic Association", - "pubYear": "2023", - "date": "2023-05-24", - "isOpenAccess": "N", - "keywords": "Diabetes; Ethnicity; Inequality; Dkd", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.

Methods

A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation.

Results

Of the 2.3\u2009million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90\u2009mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58\u2009mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5\u2009mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97).

Conclusions

There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1111/dme.15153" - }, { "id": "33692093", "doi": "https://doi.org/10.1136/heartjnl-2020-318557", @@ -15095,6 +15129,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/heartjnl-2020-318557; html:https://europepmc.org/articles/PMC8142420; pdf:https://europepmc.org/articles/PMC8142420?pdf=render" }, + { + "id": "37223892", + "doi": "https://doi.org/10.1111/dme.15153", + "title": "Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.", + "authorString": "Phillips K, Hazlehurst JM, Sheppard C, Bellary S, Hanif W, Karamat MA, Crowe FL, Stone A, Thomas GN, Peracha J, Fenton A, Sainsbury C, Nirantharakumar K, Dasgupta I.", + "authorAffiliations": "", + "journalTitle": "Diabetic medicine : a journal of the British Diabetic Association", + "pubYear": "2023", + "date": "2023-05-24", + "isOpenAccess": "N", + "keywords": "Diabetes; Ethnicity; Inequality; Dkd", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.

Methods

A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation.

Results

Of the 2.3\u2009million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90\u2009mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58\u2009mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5\u2009mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97).

Conclusions

There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/dme.15153" + }, { "id": "32896935", "doi": "https://doi.org/10.1002/cbm.2166", @@ -15129,23 +15180,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/emermed-2019-209368" }, - { - "id": "36426221", - "doi": "https://doi.org/10.3389/fcvm.2022.1016032", - "title": "Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging.", - "authorString": "Szabo L, Raisi-Estabragh Z, Salih A, McCracken C, Ruiz Pujadas E, Gkontra P, Kiss M, Maurovich-Horvath P, Vago H, Merkely B, Lee AM, Lekadir K, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Frontiers in cardiovascular medicine", - "pubYear": "2022", - "date": "2022-11-08", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Trustworthiness; Cardiovascular Imaging; Machine Learning (Ml); Ai Risk", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their \"trustworthiness\" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a \"trustworthy AI system.\" We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?pdf=render" - }, { "id": "35151869", "doi": "https://doi.org/10.1016/j.jbi.2022.104010", @@ -15163,6 +15197,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882" }, + { + "id": "36426221", + "doi": "https://doi.org/10.3389/fcvm.2022.1016032", + "title": "Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging.", + "authorString": "Szabo L, Raisi-Estabragh Z, Salih A, McCracken C, Ruiz Pujadas E, Gkontra P, Kiss M, Maurovich-Horvath P, Vago H, Merkely B, Lee AM, Lekadir K, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "Frontiers in cardiovascular medicine", + "pubYear": "2022", + "date": "2022-11-08", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Trustworthiness; Cardiovascular Imaging; Machine Learning (Ml); Ai Risk", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their \"trustworthiness\" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a \"trustworthy AI system.\" We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?pdf=render" + }, { "id": "32728709", "doi": "https://doi.org/10.1093/pubmed/fdaa115", @@ -15418,23 +15469,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1080/09638288.2021.2008526" }, - { - "id": "36660920", - "doi": "https://doi.org/10.1093/ehjci/jeac270", - "title": "The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.", - "authorString": "Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Cardiovascular Imaging", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "Y", - "keywords": "Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render" - }, { "id": "33820530", "doi": "https://doi.org/10.1186/s12916-021-01940-7", @@ -15452,6 +15486,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render; pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7" }, + { + "id": "36660920", + "doi": "https://doi.org/10.1093/ehjci/jeac270", + "title": "The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.", + "authorString": "Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Cardiovascular Imaging", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "Y", + "keywords": "Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render" + }, { "id": "34270458", "doi": "https://doi.org/10.4269/ajtmh.21-0482", @@ -15554,23 +15605,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jtha.2023.05.012" }, - { - "id": "37218687", - "doi": "https://doi.org/10.1093/ehjqcco/qcad029", - "title": "Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.", - "authorString": "Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Quality of care & clinical outcomes", - "pubYear": "2023", - "date": "2023-05-22", - "isOpenAccess": "N", - "keywords": "Myocardial infarction; Stroke; Sex differences; risk factors", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363\u00a0313 participants (53.5% women), 8\u00a0470 experienced MI (29.9% women) and 7\u00a0705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ehjqcco/qcad029; pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf" - }, { "id": "33678589", "doi": "https://doi.org/10.1016/s2589-7500(20)30317-4", @@ -15588,6 +15622,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(20)30317-4" }, + { + "id": "37218687", + "doi": "https://doi.org/10.1093/ehjqcco/qcad029", + "title": "Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.", + "authorString": "Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Quality of care & clinical outcomes", + "pubYear": "2023", + "date": "2023-05-22", + "isOpenAccess": "N", + "keywords": "Myocardial infarction; Stroke; Sex differences; risk factors", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363\u00a0313 participants (53.5% women), 8\u00a0470 experienced MI (29.9% women) and 7\u00a0705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ehjqcco/qcad029; pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf" + }, { "id": "35589356", "doi": "https://doi.org/10.1136/bmjopen-2021-057343", @@ -16047,23 +16098,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render" }, - { - "id": "37198478", - "doi": "https://doi.org/10.1038/s41586-023-06034-3", - "title": "GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.", - "authorString": "Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2023", - "date": "2023-05-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render; pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf" - }, { "id": "32771960", "doi": "https://doi.org/10.1016/j.ijmedinf.2020.104237", @@ -16098,6 +16132,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(20)30219-3; html:https://europepmc.org/articles/PMC8212701; pdf:https://europepmc.org/articles/PMC8212701?pdf=render" }, + { + "id": "37198478", + "doi": "https://doi.org/10.1038/s41586-023-06034-3", + "title": "GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.", + "authorString": "Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2023", + "date": "2023-05-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render; pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf" + }, { "id": "36545688", "doi": "https://doi.org/10.1192/bjb.2022.83", @@ -16166,6 +16217,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render; pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3" }, + { + "id": "33655079", + "doi": "https://doi.org/10.12688/wellcomeopenres.16304.2", + "title": "Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.", + "authorString": "Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2020", + "date": "2020-01-01", + "isOpenAccess": "Y", + "keywords": "Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Swab Test; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render" + }, { "id": "37634573", "doi": "https://doi.org/10.1016/j.cardfail.2023.08.008", @@ -16200,23 +16268,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.06.011; html:https://europepmc.org/articles/PMC10102720; pdf:https://europepmc.org/articles/PMC10102720?pdf=render" }, - { - "id": "33655079", - "doi": "https://doi.org/10.12688/wellcomeopenres.16304.2", - "title": "Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.", - "authorString": "Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2020", - "date": "2020-01-01", - "isOpenAccess": "Y", - "keywords": "Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Swab Test; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render" - }, { "id": "34230034", "doi": "https://doi.org/10.1136/bmjresp-2021-000967", @@ -16370,23 +16421,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph181910265; html:https://europepmc.org/articles/PMC8507693; pdf:https://europepmc.org/articles/PMC8507693?pdf=render" }, - { - "id": "34781301", - "doi": "https://doi.org/10.1159/000520674", - "title": "Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.", - "authorString": "Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.", - "authorAffiliations": "", - "journalTitle": "Cardiology", - "pubYear": "2022", - "date": "2021-11-15", - "isOpenAccess": "N", - "keywords": "Data Sources; cardiovascular; Real-world Data; Real-world Evidence", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674" - }, { "id": "30532623", "doi": "https://doi.org/10.3897/bdj.6.e29232", @@ -16404,6 +16438,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render" }, + { + "id": "34781301", + "doi": "https://doi.org/10.1159/000520674", + "title": "Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.", + "authorString": "Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.", + "authorAffiliations": "", + "journalTitle": "Cardiology", + "pubYear": "2022", + "date": "2021-11-15", + "isOpenAccess": "N", + "keywords": "Data Sources; cardiovascular; Real-world Data; Real-world Evidence", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674" + }, { "id": "35403174", "doi": "https://doi.org/10.14218/jctp.2022.00003", @@ -16659,23 +16710,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render" }, - { - "id": "35038301", - "doi": "https://doi.org/10.2196/30523", - "title": "Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.", - "authorString": "Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.", - "authorAffiliations": "", - "journalTitle": "JMIR human factors", - "pubYear": "2022", - "date": "2022-04-13", - "isOpenAccess": "Y", - "keywords": "Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Covid-19; Human-centered Design", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380; pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF" - }, { "id": "31529485", "doi": "https://doi.org/10.1111/bjd.18526", @@ -16693,6 +16727,23 @@ "laySummary": "This study investiages whether there is a smoking and socioeconomic status is linked to the risk of developing melanoma (a skin cancer). They used a Welsh database to find data on individuals who had melanoma and linked this data with smoking status and socioeconomic status on other national databases. They found that melanoma was less likely in those who smoked, but was associated with less chance of survival (due to health problems other than melanoma). Those in higher socioeconomic status had overall higher likelihood of survival.", "urls": "doi:https://doi.org/10.1111/bjd.18526; html:https://europepmc.org/articles/PMC7383980; pdf:https://europepmc.org/articles/PMC7383980?pdf=render" }, + { + "id": "35038301", + "doi": "https://doi.org/10.2196/30523", + "title": "Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.", + "authorString": "Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.", + "authorAffiliations": "", + "journalTitle": "JMIR human factors", + "pubYear": "2022", + "date": "2022-04-13", + "isOpenAccess": "Y", + "keywords": "Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Covid-19; Human-centered Design", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380; pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF" + }, { "id": "37269003", "doi": "https://doi.org/10.1186/s13643-023-02261-x", @@ -16727,23 +16778,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ehjdh/ztad037; html:https://europepmc.org/articles/PMC10393938; pdf:https://europepmc.org/articles/PMC10393938?pdf=render" }, - { - "id": "37563721", - "doi": "https://doi.org/10.1186/s13063-023-07473-z", - "title": "Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.", - "authorString": "McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.", - "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2023", - "date": "2023-08-10", - "isOpenAccess": "Y", - "keywords": "Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (\"cluster\") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render" - }, { "id": "36134690", "doi": "https://doi.org/10.1242/dev.200654", @@ -16762,21 +16796,21 @@ "urls": "doi:https://doi.org/10.1242/dev.200654; pdf:https://journals.biologists.com/dev/article-pdf/149/18/dev200654/2167548/dev200654.pdf" }, { - "id": "36763324", - "doi": "https://doi.org/10.1007/s12687-023-00635-1", - "title": "What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.", - "authorString": "Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.", + "id": "37563721", + "doi": "https://doi.org/10.1186/s13063-023-07473-z", + "title": "Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.", + "authorString": "McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.", "authorAffiliations": "", - "journalTitle": "Journal of community genetics", + "journalTitle": "Trials", "pubYear": "2023", - "date": "2023-02-10", - "isOpenAccess": "N", - "keywords": "", + "date": "2023-08-10", + "isOpenAccess": "Y", + "keywords": "Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge", "nationalPriorities": "", "healthCategories": "", - "abstract": "The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.", + "abstract": "

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (\"cluster\") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.", "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s12687-023-00635-1; pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf" + "urls": "doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render" }, { "id": "30659777", @@ -16795,6 +16829,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render" }, + { + "id": "36763324", + "doi": "https://doi.org/10.1007/s12687-023-00635-1", + "title": "What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.", + "authorString": "Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.", + "authorAffiliations": "", + "journalTitle": "Journal of community genetics", + "pubYear": "2023", + "date": "2023-02-10", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s12687-023-00635-1; pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf" + }, { "id": "35595677", "doi": "https://doi.org/10.1016/s2589-7500(22)00061-9", @@ -16897,23 +16948,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0287264; html:https://europepmc.org/articles/PMC10270623; pdf:https://europepmc.org/articles/PMC10270623?pdf=render" }, - { - "id": "37101398", - "doi": "https://doi.org/10.1002/ejhf.2868", - "title": "Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.", - "authorString": "Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.", - "authorAffiliations": "", - "journalTitle": "European journal of heart failure", - "pubYear": "2023", - "date": "2023-05-18", - "isOpenAccess": "N", - "keywords": "Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n\u2009=\u200916\u2009917; 21.7% females), registry patients eligible for RCT inclusion (n\u2009=\u200926\u2009104; 31.8% females), and registry patients ineligible for RCT inclusion (n\u2009=\u200920\u2009810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1\u2009year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/ejhf.2868" - }, { "id": "32249120", "doi": "https://doi.org/10.1016/j.schres.2020.03.044", @@ -16931,6 +16965,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.schres.2020.03.044" }, + { + "id": "37101398", + "doi": "https://doi.org/10.1002/ejhf.2868", + "title": "Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.", + "authorString": "Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.", + "authorAffiliations": "", + "journalTitle": "European journal of heart failure", + "pubYear": "2023", + "date": "2023-05-18", + "isOpenAccess": "N", + "keywords": "Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n\u2009=\u200916\u2009917; 21.7% females), registry patients eligible for RCT inclusion (n\u2009=\u200926\u2009104; 31.8% females), and registry patients ineligible for RCT inclusion (n\u2009=\u200920\u2009810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1\u2009year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1002/ejhf.2868" + }, { "id": "36810251", "doi": "https://doi.org/10.1172/jci.insight.156643", @@ -17169,23 +17220,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable" }, - { - "id": "36729586", - "doi": "https://doi.org/10.2196/42965", - "title": "Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.", - "authorString": "Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.", - "authorAffiliations": "", - "journalTitle": "JMIR research protocols", - "pubYear": "2023", - "date": "2023-02-02", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.

Objective

The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.

Methods

We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.

Results

This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.

Conclusions

This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.

International registered report identifier (irrid)

PRR1-10.2196/42965.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366" - }, { "id": "33342219", "doi": "https://doi.org/10.1161/circoutcomes.120.007085", @@ -17220,6 +17254,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571" }, + { + "id": "36729586", + "doi": "https://doi.org/10.2196/42965", + "title": "Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.", + "authorString": "Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.", + "authorAffiliations": "", + "journalTitle": "JMIR research protocols", + "pubYear": "2023", + "date": "2023-02-02", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.

Objective

The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.

Methods

We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.

Results

This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.

Conclusions

This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.

International registered report identifier (irrid)

PRR1-10.2196/42965.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366" + }, { "id": "34125897", "doi": "https://doi.org/10.1093/nar/gkab449", @@ -17237,23 +17288,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render" }, - { - "id": "37190768", - "doi": "https://doi.org/10.1017/s2045796023000276", - "title": "The mental health of all children in contact with social services: a population-wide record-linkage study in Northern Ireland.", - "authorString": "McKenna S, O'Reilly D, Maguire A.", - "authorAffiliations": "", - "journalTitle": "Epidemiology and psychiatric sciences", - "pubYear": "2023", - "date": "2023-05-16", - "isOpenAccess": "Y", - "keywords": "Mental health; Data Linkage; Children\u2019s Social Care", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Children in contact with social services are at high risk for mental ill health, but it is not known what proportion of the child population has contact with social services or how risk varies within this group compared to unexposed peers. We aim to quantify the extent and nature of contact with social services within the child population in Northern Ireland (NI) and the association with mental ill health. We also examine which social care experiences identify those most at risk.

Methods

This is a population-based record-linkage study of 497,269 children (aged under 18\u00a0years) alive and resident in NI in 2015 using routinely collected health and social care data. Exposure was categorized as (1) no contact, (2) referred but assessed as not in need (NIN), (3) child in need (CIN) and (4) child in care (CIC). Multilevel logistic regression analyses estimated odds ratios (ORs) for mental ill health indicated by receipt of psychotropic medication (antidepressants, anxiolytics, antipsychotics and hypnotics), psychiatric hospital admission and hospital-presenting self-harm or ideation.

Results

Over one in six children (17.2%, n\u00a0=\u00a085,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, n\u00a0=\u00a023,975) had contact in 2015. Likelihood of any mental ill health outcome increased incrementally with the level of contact with social services relative to unexposed peers: NIN (OR 5.90 [95% confidence interval (CI) 5.10-6.83]), CIN (OR 5.99 [95% CI 5.50-6.53]) and CIC (OR 12.60 [95% CI 10.63-14.95]). All tiers of contact, number of referrals, number of care episodes and placement type were strongly associated with the likelihood of mental ill health.

Conclusion

Children who have contact with social services account for a large and disproportionate amount of mental ill health in the child population. Likelihood of poor mental health across indicators is highest in care experienced children but also extends to the much larger population of children in contact with social services but never in care. Findings suggest a need for targeted mental health screening and enhanced support for all children in contact with social services.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render" - }, { "id": "32975552", "doi": "https://doi.org/10.1001/jamapediatrics.2020.4573", @@ -17271,6 +17305,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573" }, + { + "id": "37190768", + "doi": "https://doi.org/10.1017/s2045796023000276", + "title": "The mental health of all children in contact with social services: a population-wide record-linkage study in Northern Ireland.", + "authorString": "McKenna S, O'Reilly D, Maguire A.", + "authorAffiliations": "", + "journalTitle": "Epidemiology and psychiatric sciences", + "pubYear": "2023", + "date": "2023-05-16", + "isOpenAccess": "Y", + "keywords": "Mental health; Data Linkage; Children\u2019s Social Care", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Children in contact with social services are at high risk for mental ill health, but it is not known what proportion of the child population has contact with social services or how risk varies within this group compared to unexposed peers. We aim to quantify the extent and nature of contact with social services within the child population in Northern Ireland (NI) and the association with mental ill health. We also examine which social care experiences identify those most at risk.

Methods

This is a population-based record-linkage study of 497,269 children (aged under 18\u00a0years) alive and resident in NI in 2015 using routinely collected health and social care data. Exposure was categorized as (1) no contact, (2) referred but assessed as not in need (NIN), (3) child in need (CIN) and (4) child in care (CIC). Multilevel logistic regression analyses estimated odds ratios (ORs) for mental ill health indicated by receipt of psychotropic medication (antidepressants, anxiolytics, antipsychotics and hypnotics), psychiatric hospital admission and hospital-presenting self-harm or ideation.

Results

Over one in six children (17.2%, n\u00a0=\u00a085,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, n\u00a0=\u00a023,975) had contact in 2015. Likelihood of any mental ill health outcome increased incrementally with the level of contact with social services relative to unexposed peers: NIN (OR 5.90 [95% confidence interval (CI) 5.10-6.83]), CIN (OR 5.99 [95% CI 5.50-6.53]) and CIC (OR 12.60 [95% CI 10.63-14.95]). All tiers of contact, number of referrals, number of care episodes and placement type were strongly associated with the likelihood of mental ill health.

Conclusion

Children who have contact with social services account for a large and disproportionate amount of mental ill health in the child population. Likelihood of poor mental health across indicators is highest in care experienced children but also extends to the much larger population of children in contact with social services but never in care. Findings suggest a need for targeted mental health screening and enhanced support for all children in contact with social services.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render" + }, { "id": "30729733", "doi": "https://doi.org/10.1111/ijpo.12512", @@ -17390,23 +17441,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ajcn/nqaa266" }, - { - "id": "37072241", - "doi": "https://doi.org/10.1136/heartjnl-2022-321888", - "title": "Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.", - "authorString": "Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, Walter FM, Manisty CH, Robson J, Mamas MA, Harvey NC, Neubauer S, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Heart (British Cardiac Society)", - "pubYear": "2023", - "date": "2023-06-14", - "isOpenAccess": "Y", - "keywords": "epidemiology; Magnetic Resonance Imaging", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8\u00b11.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18\u2009714 participants (67%\u2009women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render; pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf" - }, { "id": "30969971", "doi": "https://doi.org/10.1371/journal.pone.0213435", @@ -17424,6 +17458,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render" }, + { + "id": "37072241", + "doi": "https://doi.org/10.1136/heartjnl-2022-321888", + "title": "Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.", + "authorString": "Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, Walter FM, Manisty CH, Robson J, Mamas MA, Harvey NC, Neubauer S, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "Heart (British Cardiac Society)", + "pubYear": "2023", + "date": "2023-06-14", + "isOpenAccess": "Y", + "keywords": "epidemiology; Magnetic Resonance Imaging", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8\u00b11.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18\u2009714 participants (67%\u2009women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render; pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf" + }, { "id": "36929232", "doi": "https://doi.org/10.1002/jmri.28675", @@ -17594,23 +17645,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render; pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf" }, - { - "id": "37538742", - "doi": "https://doi.org/10.1098/rsos.221469", - "title": "Bayesian inference of polymerase dynamics over the exclusion process.", - "authorString": "Cavallaro M, Wang Y, Hebenstreit D, Dutta R.", - "authorAffiliations": "", - "journalTitle": "Royal Society open science", - "pubYear": "2023", - "date": "2023-08-02", - "isOpenAccess": "Y", - "keywords": "Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render" - }, { "id": "35487318", "doi": "https://doi.org/10.1016/j.ijcard.2022.04.067", @@ -17628,6 +17662,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijcard.2022.04.067" }, + { + "id": "37538742", + "doi": "https://doi.org/10.1098/rsos.221469", + "title": "Bayesian inference of polymerase dynamics over the exclusion process.", + "authorString": "Cavallaro M, Wang Y, Hebenstreit D, Dutta R.", + "authorAffiliations": "", + "journalTitle": "Royal Society open science", + "pubYear": "2023", + "date": "2023-08-02", + "isOpenAccess": "Y", + "keywords": "Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render" + }, { "id": "36355406", "doi": "https://doi.org/10.2196/40707", @@ -17713,23 +17764,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1080/17434440.2022.2132147" }, - { - "id": "35022215", - "doi": "https://doi.org/10.1136/bmj-2021-067519", - "title": "Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.", - "authorString": "Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.", - "authorAffiliations": "", - "journalTitle": "BMJ (Clinical research ed.)", - "pubYear": "2022", - "date": "2022-01-12", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51\u2009655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render" - }, { "id": "35440446", "doi": "https://doi.org/10.1136/bmjopen-2021-052514", @@ -17747,6 +17781,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render" }, + { + "id": "35022215", + "doi": "https://doi.org/10.1136/bmj-2021-067519", + "title": "Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.", + "authorString": "Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.", + "authorAffiliations": "", + "journalTitle": "BMJ (Clinical research ed.)", + "pubYear": "2022", + "date": "2022-01-12", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51\u2009655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render" + }, { "id": "33766511", "doi": "https://doi.org/10.1016/j.jid.2021.02.744", @@ -17849,23 +17900,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1" }, - { - "id": "36243582", - "doi": "https://doi.org/10.1016/j.injury.2022.09.052", - "title": "Older trauma patients with isolated chest injuries have low rates of complications.", - "authorString": "Ferrah N, Beck B, Ibrahim J, Gabbe B, McLellan MS, Cameron P.", - "authorAffiliations": "", - "journalTitle": "Injury", - "pubYear": "2022", - "date": "2022-10-07", - "isOpenAccess": "N", - "keywords": "Geriatric; Complication; Pneumonia; Chest Trauma; Older; Trauma Centre", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The number of older adults hospitalised for injury is growing rapidly. The population-adjusted incidence of isolated thoracic injuries in older adults is also growing. While some older adults are at high risk of post-traumatic complications, not all older adults will need treatment in a major trauma service (MTS). The aim of this study was to characterise older patients with isolated chest injuries, determine the rates of post-traumatic complications, including respiratory failure and pneumonia, and the factors associated with the risk of developing these complications.

Patients and methods

This was a retrospective review of patients aged 65 years and over with isolated chest trauma, from January 2007 to June 2017, using data from the Victorian State Trauma Registry. Patient characteristics and rates of complications were compared between patients with 1. isolated rib fractures, and 2. complex chest injury. Multivariable logistic regression was used to identify predictors of respiratory failure, and pneumonia.

Results

The study population comprised 5401 patients aged 65 years or more, with isolated chest injuries. Two-thirds (65%) of all patients had isolated rib fractures, and 58% of patients (n\u00a0=\u00a03156) were directly admitted to a non-major trauma centre. Complications were uncommon, with 5.45% of all patients (n\u00a0=\u00a0295) having pneumonia and 3.2% (n\u00a0=\u00a0175) having respiratory failure. Factors associated with increased risk of pneumonia and respiratory failure included advancing age, smoking, chronic obstructive pulmonary disease, congestive heart failure, and more severe and complex chest injury. The adjusted odds of complications were lowest amongst patients not classified as major trauma and receiving definitive treatment in non-MTS.

Discussion

Our findings suggest that rates of complications in older patients with isolated chest trauma in this study were low, and that there is a large group of patients with isolated, uncomplicated rib fractures, who may not need to be treated in a major trauma centre. Further work should be undertaken to appropriately risk stratify and manage older adults with isolated chest trauma.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.injury.2022.09.052" - }, { "id": "31194737", "doi": "https://doi.org/10.1371/journal.pgen.1008164", @@ -17883,6 +17917,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?pdf=render" }, + { + "id": "36243582", + "doi": "https://doi.org/10.1016/j.injury.2022.09.052", + "title": "Older trauma patients with isolated chest injuries have low rates of complications.", + "authorString": "Ferrah N, Beck B, Ibrahim J, Gabbe B, McLellan MS, Cameron P.", + "authorAffiliations": "", + "journalTitle": "Injury", + "pubYear": "2022", + "date": "2022-10-07", + "isOpenAccess": "N", + "keywords": "Geriatric; Complication; Pneumonia; Chest Trauma; Older; Trauma Centre", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

The number of older adults hospitalised for injury is growing rapidly. The population-adjusted incidence of isolated thoracic injuries in older adults is also growing. While some older adults are at high risk of post-traumatic complications, not all older adults will need treatment in a major trauma service (MTS). The aim of this study was to characterise older patients with isolated chest injuries, determine the rates of post-traumatic complications, including respiratory failure and pneumonia, and the factors associated with the risk of developing these complications.

Patients and methods

This was a retrospective review of patients aged 65 years and over with isolated chest trauma, from January 2007 to June 2017, using data from the Victorian State Trauma Registry. Patient characteristics and rates of complications were compared between patients with 1. isolated rib fractures, and 2. complex chest injury. Multivariable logistic regression was used to identify predictors of respiratory failure, and pneumonia.

Results

The study population comprised 5401 patients aged 65 years or more, with isolated chest injuries. Two-thirds (65%) of all patients had isolated rib fractures, and 58% of patients (n\u00a0=\u00a03156) were directly admitted to a non-major trauma centre. Complications were uncommon, with 5.45% of all patients (n\u00a0=\u00a0295) having pneumonia and 3.2% (n\u00a0=\u00a0175) having respiratory failure. Factors associated with increased risk of pneumonia and respiratory failure included advancing age, smoking, chronic obstructive pulmonary disease, congestive heart failure, and more severe and complex chest injury. The adjusted odds of complications were lowest amongst patients not classified as major trauma and receiving definitive treatment in non-MTS.

Discussion

Our findings suggest that rates of complications in older patients with isolated chest trauma in this study were low, and that there is a large group of patients with isolated, uncomplicated rib fractures, who may not need to be treated in a major trauma centre. Further work should be undertaken to appropriately risk stratify and manage older adults with isolated chest trauma.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.injury.2022.09.052" + }, { "id": "36669843", "doi": "https://doi.org/10.1136/bmjopen-2022-064364", @@ -17951,23 +18002,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/20552076211048654; html:https://europepmc.org/articles/PMC8637703; pdf:https://europepmc.org/articles/PMC8637703?pdf=render" }, - { - "id": "36828608", - "doi": "https://doi.org/10.1016/s2589-7500(22)00249-7", - "title": "The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).", - "authorString": "Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2023", - "date": "2023-03-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00249-7" - }, { "id": "33130851", "doi": "https://doi.org/10.1093/ije/dyaa216", @@ -18003,21 +18037,21 @@ "urls": "doi:https://doi.org/10.1136/thoraxjnl-2020-215566" }, { - "id": "36929968", - "doi": "https://doi.org/10.1016/s0140-6736(22)02235-8", - "title": "Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.", - "authorString": "Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.", + "id": "36828608", + "doi": "https://doi.org/10.1016/s2589-7500(22)00249-7", + "title": "The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).", + "authorString": "Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.", "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2022", - "date": "2022-11-24", - "isOpenAccess": "Y", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2023", + "date": "2023-03-01", + "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60\u00b74% vs 62\u00b77%; p<0\u00b7001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.", + "abstract": "The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render" + "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00249-7" }, { "id": "33382071", @@ -18036,6 +18070,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/schbul/sbaa176; html:https://europepmc.org/articles/PMC7965055; pdf:https://europepmc.org/articles/PMC7965055?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa176" }, + { + "id": "36929968", + "doi": "https://doi.org/10.1016/s0140-6736(22)02235-8", + "title": "Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.", + "authorString": "Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2022", + "date": "2022-11-24", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60\u00b74% vs 62\u00b77%; p<0\u00b7001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render" + }, { "id": "36854461", "doi": "https://doi.org/10.1136/bmj-2022-073149", @@ -18121,23 +18172,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/cpz1.373" }, - { - "id": "34907415", - "doi": "https://doi.org/10.1093/ehjci/jeab266", - "title": "Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.", - "authorString": "Raisi-Estabragh Z, McCracken C, Condurache D, Aung N, Vargas JD, Naderi H, Munroe PB, Neubauer S, Harvey NC, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Cardiovascular Imaging", - "pubYear": "2022", - "date": "2022-08-01", - "isOpenAccess": "Y", - "keywords": "Mortality; Atrial fibrillation; Stroke; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Left ventricle; Vascular Risk Factors; Cardiovascular Outcomes; Lef; T Atrium", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.

Methods and results

We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.

Conclusion

LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render" - }, { "id": "32071531", "doi": "https://doi.org/10.1016/j.jor.2020.02.001", @@ -18155,6 +18189,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jor.2020.02.001; html:https://europepmc.org/articles/PMC7016330; pdf:https://europepmc.org/articles/PMC7016330?pdf=render; doi:https://doi.org/10.1016/j.jor.2020.02.001" }, + { + "id": "34907415", + "doi": "https://doi.org/10.1093/ehjci/jeab266", + "title": "Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.", + "authorString": "Raisi-Estabragh Z, McCracken C, Condurache D, Aung N, Vargas JD, Naderi H, Munroe PB, Neubauer S, Harvey NC, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Cardiovascular Imaging", + "pubYear": "2022", + "date": "2022-08-01", + "isOpenAccess": "Y", + "keywords": "Mortality; Atrial fibrillation; Stroke; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Left ventricle; Vascular Risk Factors; Cardiovascular Outcomes; Lef; T Atrium", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.

Methods and results

We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.

Conclusion

LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render" + }, { "id": "34000735", "doi": "https://doi.org/10.1093/ije/dyab025", @@ -18462,21 +18513,21 @@ "urls": "doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render" }, { - "id": "37348153", - "doi": "https://doi.org/10.1016/j.amjcard.2023.05.039", - "title": "Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.", - "authorString": "Althunayyan A, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.", + "id": "35242820", + "doi": "https://doi.org/10.3389/fcvm.2021.816985", + "title": "A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms.", + "authorString": "Rauseo E, Omer M, Amir-Khalili A, Sojoudi A, Le TT, Cook SA, Hausenloy DJ, Ang B, Toh DF, Bryant J, Chin CWL, Paiva JM, Fung K, Cooper J, Khanji MY, Aung N, Petersen SE.", "authorAffiliations": "", - "journalTitle": "The American journal of cardiology", - "pubYear": "2023", - "date": "2023-06-20", - "isOpenAccess": "N", - "keywords": "", + "journalTitle": "Frontiers in cardiovascular medicine", + "pubYear": "2021", + "date": "2022-02-15", + "isOpenAccess": "Y", + "keywords": "Quality control; Assessment; Machine Learning; Cardiac Segmentation; Cardiac Magnetic Resonance (Cmr); Automated Contouring", "nationalPriorities": "", "healthCategories": "", - "abstract": "The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24\u00a0months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2\u00a0years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p\u00a0=\u00a00.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p\u00a0=\u00a00.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p\u00a0=\u00a00.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p\u00a0=\u00a00.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.", + "abstract": "

Background

The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed.

Objective

We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm.

Methods

A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease.

Results

The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension.

Conclusions

Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.amjcard.2023.05.039" + "urls": "doi:https://doi.org/10.3389/fcvm.2021.816985; html:https://europepmc.org/articles/PMC8886212; pdf:https://europepmc.org/articles/PMC8886212?pdf=render" }, { "id": "35748342", @@ -18496,21 +18547,21 @@ "urls": "doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render" }, { - "id": "35242820", - "doi": "https://doi.org/10.3389/fcvm.2021.816985", - "title": "A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms.", - "authorString": "Rauseo E, Omer M, Amir-Khalili A, Sojoudi A, Le TT, Cook SA, Hausenloy DJ, Ang B, Toh DF, Bryant J, Chin CWL, Paiva JM, Fung K, Cooper J, Khanji MY, Aung N, Petersen SE.", + "id": "37348153", + "doi": "https://doi.org/10.1016/j.amjcard.2023.05.039", + "title": "Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.", + "authorString": "Althunayyan A, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.", "authorAffiliations": "", - "journalTitle": "Frontiers in cardiovascular medicine", - "pubYear": "2021", - "date": "2022-02-15", - "isOpenAccess": "Y", - "keywords": "Quality control; Assessment; Machine Learning; Cardiac Segmentation; Cardiac Magnetic Resonance (Cmr); Automated Contouring", + "journalTitle": "The American journal of cardiology", + "pubYear": "2023", + "date": "2023-06-20", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed.

Objective

We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm.

Methods

A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease.

Results

The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension.

Conclusions

Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.", + "abstract": "The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24\u00a0months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2\u00a0years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p\u00a0=\u00a00.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p\u00a0=\u00a00.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p\u00a0=\u00a00.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p\u00a0=\u00a00.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.", "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fcvm.2021.816985; html:https://europepmc.org/articles/PMC8886212; pdf:https://europepmc.org/articles/PMC8886212?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.amjcard.2023.05.039" }, { "id": "35202588", @@ -18733,23 +18784,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0240902; html:https://europepmc.org/articles/PMC7660485; pdf:https://europepmc.org/articles/PMC7660485?pdf=render" }, - { - "id": "32282926", - "doi": "https://doi.org/10.1111/bjd.19122", - "title": "Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark.", - "authorString": "Wong AYS, Kjaersgaard A, Fr\u00f8slev T, Forbes HJ, Mansfield KE, Silverwood RJ, S\u00f8rensen HT, Smeeth L, Schmidt SAJ, Langan SM.", - "authorAffiliations": "", - "journalTitle": "The British journal of dermatology", - "pubYear": "2020", - "date": "2020-06-10", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1111/bjd.19122" - }, { "id": "30909231", "doi": "https://doi.org/10.3233/jad-181085", @@ -18767,6 +18801,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3233/JAD-181085; html:https://europepmc.org/articles/PMC6484273; pdf:https://europepmc.org/articles/PMC6484273?pdf=render" }, + { + "id": "32282926", + "doi": "https://doi.org/10.1111/bjd.19122", + "title": "Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark.", + "authorString": "Wong AYS, Kjaersgaard A, Fr\u00f8slev T, Forbes HJ, Mansfield KE, Silverwood RJ, S\u00f8rensen HT, Smeeth L, Schmidt SAJ, Langan SM.", + "authorAffiliations": "", + "journalTitle": "The British journal of dermatology", + "pubYear": "2020", + "date": "2020-06-10", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/bjd.19122" + }, { "id": "36344532", "doi": "https://doi.org/10.1038/s41598-022-21663-w", @@ -18954,23 +19005,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286" }, - { - "id": "36082669", - "doi": "https://doi.org/10.1161/hypertensionaha.122.19354", - "title": "Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.", - "authorString": "Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.", - "authorAffiliations": "", - "journalTitle": "Hypertension (Dallas, Tex. : 1979)", - "pubYear": "2022", - "date": "2022-09-09", - "isOpenAccess": "Y", - "keywords": "Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio \u22653 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR \u2265120 mL (min\u00b71.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15\u2009500 with albuminuria. 1828 participants had an eGFR \u2265120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR \u226560 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render" - }, { "id": "35579056", "doi": "https://doi.org/10.1111/eci.13814", @@ -18988,6 +19022,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/eci.13814; html:https://europepmc.org/articles/PMC9540114; pdf:https://europepmc.org/articles/PMC9540114?pdf=render" }, + { + "id": "36082669", + "doi": "https://doi.org/10.1161/hypertensionaha.122.19354", + "title": "Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.", + "authorString": "Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.", + "authorAffiliations": "", + "journalTitle": "Hypertension (Dallas, Tex. : 1979)", + "pubYear": "2022", + "date": "2022-09-09", + "isOpenAccess": "Y", + "keywords": "Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio \u22653 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR \u2265120 mL (min\u00b71.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15\u2009500 with albuminuria. 1828 participants had an eGFR \u2265120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR \u226560 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render" + }, { "id": "32861307", "doi": "https://doi.org/10.1016/s0140-6736(20)30930-2", @@ -19039,23 +19090,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render" }, - { - "id": "36991119", - "doi": "https://doi.org/10.1038/s41586-023-05844-9", - "title": "An atlas of genetic scores to predict multi-omic traits.", - "authorString": "Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson \u00c5, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, M\u00e4larstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2023", - "date": "2023-03-29", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n\u2009=\u200950,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n\u2009=\u20093,175; Olink, n\u2009=\u20094,822), plasma metabolomics (Metabolon HD4, n\u2009=\u20098,153), serum metabolomics (Nightingale, n\u2009=\u200937,359) and whole-blood Illumina RNA sequencing (n\u2009=\u20094,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41586-023-05844-9; pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf" - }, { "id": "34849869", "doi": "https://doi.org/10.1093/gigascience/giab076", @@ -19073,6 +19107,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render" }, + { + "id": "36991119", + "doi": "https://doi.org/10.1038/s41586-023-05844-9", + "title": "An atlas of genetic scores to predict multi-omic traits.", + "authorString": "Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson \u00c5, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, M\u00e4larstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2023", + "date": "2023-03-29", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n\u2009=\u200950,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n\u2009=\u20093,175; Olink, n\u2009=\u20094,822), plasma metabolomics (Metabolon HD4, n\u2009=\u20098,153), serum metabolomics (Nightingale, n\u2009=\u200937,359) and whole-blood Illumina RNA sequencing (n\u2009=\u20094,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41586-023-05844-9; pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf" + }, { "id": "36469091", "doi": "https://doi.org/10.1093/ageing/afac252", @@ -19124,23 +19175,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ejrad.2022.110366" }, - { - "id": "35016872", - "doi": "https://doi.org/10.1016/j.apmr.2021.12.014", - "title": "Chronic Physical Health Conditions After Injury: A Comparison of Prevalence and Risk in People With Orthopedic Major Trauma and Other Types of Injury.", - "authorString": "Gelaw AY, Gabbe BJ, Ekegren CL.", - "authorAffiliations": "", - "journalTitle": "Archives of physical medicine and rehabilitation", - "pubYear": "2022", - "date": "2022-01-10", - "isOpenAccess": "N", - "keywords": "Cardiovascular diseases; Rehabilitation; Chronic disease; wounds and injuries; Multiple Trauma", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To determine (1) the prevalence of chronic physical health conditions reported preinjury, at the time of injury, up to 1 year postinjury, and 1 to 5 years postinjury; and (2) the risk of chronic physical health conditions reported 1 to 5 years postinjury in people with orthopedic and other types of major trauma.

Design

Cohort study using linked trauma registry and health administrative datasets.

Setting

This study used linked data from the Victorian State Trauma Registry (VSTR), the Victorian Registry of Births, Deaths and Marriages (BDM), the Victorian Admitted Episodes Dataset (VAED), and the Victorian Emergency Minimum Dataset (VEMD).

Participants

Major trauma patients (N=28,522) aged 18 years and older who were registered by the VSTR, with dates of injury from 2007 to 2016, and who survived to at least 1 year after injury, were included in this study. Major trauma cases were classified into 4 groups: (1) orthopedic injury, (2) severe traumatic brain injury (s-TBI), (3) spinal cord injury, and (4) other major trauma.

Intervention

Not applicable.

Main outcome measure

Prevalence of chronic physical health conditions.

Results

The cumulative prevalence of any chronic physical health condition for all participants was 69.3%. The s-TBI group had the highest cumulative prevalence of conditions. The most common conditions were arthritis and arthropathies, cancer, and cardiovascular diseases. Preinjury chronic conditions were most common in people with s-TBI (19.3%) and were least common in people with other types of major trauma (6.6%). The highest prevalence of new-onset conditions after injury was found in people with s-TBI (21.7%) and orthopedic major trauma (21.4%), whereas the lowest prevalence was found in people with other types of major trauma (9.2%). For the orthopedic injury group, there were no significant differences in the adjusted risk of conditions reported 1 to 5 years postinjury compared with other major trauma groups.

Conclusions

Chronic physical health conditions were common among all injury groups. There was no significant difference in the risk of chronic conditions among injury groups. Rehabilitation practitioners should be aware of the risk of chronic conditions in people with orthopedic and other types of major trauma. Long-term follow-up care after injury should include prevention and treatment of chronic conditions.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.apmr.2021.12.014" - }, { "id": "31558464", "doi": "https://doi.org/10.1136/bmjopen-2019-033013", @@ -19158,6 +19192,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render" }, + { + "id": "35016872", + "doi": "https://doi.org/10.1016/j.apmr.2021.12.014", + "title": "Chronic Physical Health Conditions After Injury: A Comparison of Prevalence and Risk in People With Orthopedic Major Trauma and Other Types of Injury.", + "authorString": "Gelaw AY, Gabbe BJ, Ekegren CL.", + "authorAffiliations": "", + "journalTitle": "Archives of physical medicine and rehabilitation", + "pubYear": "2022", + "date": "2022-01-10", + "isOpenAccess": "N", + "keywords": "Cardiovascular diseases; Rehabilitation; Chronic disease; wounds and injuries; Multiple Trauma", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To determine (1) the prevalence of chronic physical health conditions reported preinjury, at the time of injury, up to 1 year postinjury, and 1 to 5 years postinjury; and (2) the risk of chronic physical health conditions reported 1 to 5 years postinjury in people with orthopedic and other types of major trauma.

Design

Cohort study using linked trauma registry and health administrative datasets.

Setting

This study used linked data from the Victorian State Trauma Registry (VSTR), the Victorian Registry of Births, Deaths and Marriages (BDM), the Victorian Admitted Episodes Dataset (VAED), and the Victorian Emergency Minimum Dataset (VEMD).

Participants

Major trauma patients (N=28,522) aged 18 years and older who were registered by the VSTR, with dates of injury from 2007 to 2016, and who survived to at least 1 year after injury, were included in this study. Major trauma cases were classified into 4 groups: (1) orthopedic injury, (2) severe traumatic brain injury (s-TBI), (3) spinal cord injury, and (4) other major trauma.

Intervention

Not applicable.

Main outcome measure

Prevalence of chronic physical health conditions.

Results

The cumulative prevalence of any chronic physical health condition for all participants was 69.3%. The s-TBI group had the highest cumulative prevalence of conditions. The most common conditions were arthritis and arthropathies, cancer, and cardiovascular diseases. Preinjury chronic conditions were most common in people with s-TBI (19.3%) and were least common in people with other types of major trauma (6.6%). The highest prevalence of new-onset conditions after injury was found in people with s-TBI (21.7%) and orthopedic major trauma (21.4%), whereas the lowest prevalence was found in people with other types of major trauma (9.2%). For the orthopedic injury group, there were no significant differences in the adjusted risk of conditions reported 1 to 5 years postinjury compared with other major trauma groups.

Conclusions

Chronic physical health conditions were common among all injury groups. There was no significant difference in the risk of chronic conditions among injury groups. Rehabilitation practitioners should be aware of the risk of chronic conditions in people with orthopedic and other types of major trauma. Long-term follow-up care after injury should include prevention and treatment of chronic conditions.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.apmr.2021.12.014" + }, { "id": "PMC9023380", "doi": "https://doi.org/", @@ -19192,23 +19243,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1155/2021/6663884; html:https://europepmc.org/articles/PMC8285182; pdf:https://europepmc.org/articles/PMC8285182?pdf=render" }, - { - "id": "37198662", - "doi": "https://doi.org/10.1186/s13293-023-00516-9", - "title": "Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure.", - "authorString": "de Bakker M, Petersen TB, Akkerhuis KM, Harakalova M, Umans VA, Germans T, Caliskan K, Katsikis PD, van der Spek PJ, Suthahar N, de Boer RA, Rizopoulos D, Asselbergs FW, Boersma E, Kardys I.", - "authorAffiliations": "", - "journalTitle": "Biology of sex differences", - "pubYear": "2023", - "date": "2023-05-17", - "isOpenAccess": "Y", - "keywords": "Proteomics; Sex differences; Heart Failure; Hfref", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.

Methods

In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13-31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.

Results

In 104 women and 278 men (mean age 62 and 64\u00a0years, respectively) cumulative PEP incidence at 30\u00a0months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction\u2009<\u20090.001) and somatostatin (Pinteraction\u2009=\u20090.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p\u2009<\u20090.001) compared to women (1.14 [1.01, 1.29], p\u2009=\u20090.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p\u2009<\u20090.001), but inversely associated in women (0.33 [0.12, 0.93], p\u2009=\u20090.036).

Conclusion

Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13293-023-00516-9; html:https://europepmc.org/articles/PMC10193800; pdf:https://europepmc.org/articles/PMC10193800?pdf=render" - }, { "id": "32929109", "doi": "https://doi.org/10.1038/s41598-020-72060-0", @@ -19226,6 +19260,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-020-72060-0; html:https://europepmc.org/articles/PMC7490405; pdf:https://europepmc.org/articles/PMC7490405?pdf=render" }, + { + "id": "37198662", + "doi": "https://doi.org/10.1186/s13293-023-00516-9", + "title": "Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure.", + "authorString": "de Bakker M, Petersen TB, Akkerhuis KM, Harakalova M, Umans VA, Germans T, Caliskan K, Katsikis PD, van der Spek PJ, Suthahar N, de Boer RA, Rizopoulos D, Asselbergs FW, Boersma E, Kardys I.", + "authorAffiliations": "", + "journalTitle": "Biology of sex differences", + "pubYear": "2023", + "date": "2023-05-17", + "isOpenAccess": "Y", + "keywords": "Proteomics; Sex differences; Heart Failure; Hfref", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.

Methods

In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13-31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.

Results

In 104 women and 278 men (mean age 62 and 64\u00a0years, respectively) cumulative PEP incidence at 30\u00a0months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction\u2009<\u20090.001) and somatostatin (Pinteraction\u2009=\u20090.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p\u2009<\u20090.001) compared to women (1.14 [1.01, 1.29], p\u2009=\u20090.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p\u2009<\u20090.001), but inversely associated in women (0.33 [0.12, 0.93], p\u2009=\u20090.036).

Conclusion

Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13293-023-00516-9; html:https://europepmc.org/articles/PMC10193800; pdf:https://europepmc.org/articles/PMC10193800?pdf=render" + }, { "id": "37422075", "doi": "https://doi.org/10.1016/j.jval.2023.06.019", @@ -19260,23 +19311,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(20)30218-1; html:https://europepmc.org/articles/PMC8183333; pdf:https://europepmc.org/articles/PMC8183333?pdf=render; doi:https://doi.org/10.1016/s2589-7500(20)30218-1" }, - { - "id": "35587337", - "doi": "https://doi.org/10.1093/ije/dyac105", - "title": "Gestational age at birth, chronic conditions and school outcomes: a population-based data linkage study of children born in England. ", - "authorString": "Libuy N, Gilbert R, Mc Grath-Lone L, Blackburn R, Etoori D, Harron K.", - "authorAffiliations": "", - "journalTitle": "International journal of epidemiology", - "pubYear": "2023", - "date": "2023-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "We aimed to generate evidence about child development measured through school attainment and provision of special educational needs (SEN) across the spectrum of gestational age, including for children born early term and >41\u2009weeks of gestation, with and without chronic health conditions. We used a national linked dataset of hospital and education records of children born in England between 1 September 2004 and 31 August 2005. We evaluated school attainment at Key Stage 1 (KS1; age 7) and Key Stage 2 (KS2; age 11) and any SEN by age 11. We stratified analyses by chronic health conditions up to age 2, and size-for-gestation, and calculated population attributable fractions (PAF). Of 306 717 children, 5.8% were born <37\u2009weeks gestation and 7.0% had a chronic condition. The percentage of children not achieving the expected level at KS1 increased from 7.6% at 41\u2009weeks, to 50.0% at 24\u2009weeks of gestation. A similar pattern was seen at KS2. SEN ranged from 29.0% at 41\u2009weeks to 82.6% at 24\u2009weeks. Children born early term (37-38\u2009weeks of gestation) had poorer outcomes than those born at 40\u2009weeks; 3.2% of children with SEN were attributable to having a chronic condition compared with 2.0% attributable to preterm birth. Children born with early identified chronic conditions contribute more to the burden of poor school outcomes than preterm birth. Evaluation is needed of how early health characteristics can be used to improve preparation for education, before and at entry to school.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render" - }, { "id": "34948912", "doi": "https://doi.org/10.3390/ijerph182413304", @@ -19294,6 +19328,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph182413304; html:https://europepmc.org/articles/PMC8707886; pdf:https://europepmc.org/articles/PMC8707886?pdf=render" }, + { + "id": "35587337", + "doi": "https://doi.org/10.1093/ije/dyac105", + "title": "Gestational age at birth, chronic conditions and school outcomes: a population-based data linkage study of children born in England. ", + "authorString": "Libuy N, Gilbert R, Mc Grath-Lone L, Blackburn R, Etoori D, Harron K.", + "authorAffiliations": "", + "journalTitle": "International journal of epidemiology", + "pubYear": "2023", + "date": "2023-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "We aimed to generate evidence about child development measured through school attainment and provision of special educational needs (SEN) across the spectrum of gestational age, including for children born early term and >41\u2009weeks of gestation, with and without chronic health conditions. We used a national linked dataset of hospital and education records of children born in England between 1 September 2004 and 31 August 2005. We evaluated school attainment at Key Stage 1 (KS1; age 7) and Key Stage 2 (KS2; age 11) and any SEN by age 11. We stratified analyses by chronic health conditions up to age 2, and size-for-gestation, and calculated population attributable fractions (PAF). Of 306 717 children, 5.8% were born <37\u2009weeks gestation and 7.0% had a chronic condition. The percentage of children not achieving the expected level at KS1 increased from 7.6% at 41\u2009weeks, to 50.0% at 24\u2009weeks of gestation. A similar pattern was seen at KS2. SEN ranged from 29.0% at 41\u2009weeks to 82.6% at 24\u2009weeks. Children born early term (37-38\u2009weeks of gestation) had poorer outcomes than those born at 40\u2009weeks; 3.2% of children with SEN were attributable to having a chronic condition compared with 2.0% attributable to preterm birth. Children born with early identified chronic conditions contribute more to the burden of poor school outcomes than preterm birth. Evaluation is needed of how early health characteristics can be used to improve preparation for education, before and at entry to school.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render" + }, { "id": "34038519", "doi": "https://doi.org/10.1093/ageing/afab084", @@ -19345,23 +19396,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00252-7" }, - { - "id": "36722341", - "doi": "https://doi.org/10.1093/cei/uxad008", - "title": "Practical challenges for functional validation of STAT1 gain of function genetic variants.", - "authorString": "Albuquerque AS, Maimaris J, McKenna AJ, Lambourne J, Moreira F, Workman S, Megy K, Simeoni I, Lango Allen H, NIHR BioResource-Rare Disease Consortium, Morris EC, Burns SO.", - "authorAffiliations": "", - "journalTitle": "Clinical and experimental immunology", - "pubYear": "2023", - "date": "2023-04-01", - "isOpenAccess": "Y", - "keywords": "Flow cytometry; STAT1; Primary Immunodeficiency; Gain Of Function; Chronic Mucocutaneous Candidiasis; Variants Of Unknown Significance", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/cei/uxad008; html:https://europepmc.org/articles/PMC10128160; pdf:https://europepmc.org/articles/PMC10128160?pdf=render" - }, { "id": "33830993", "doi": "https://doi.org/10.1371/journal.pgen.1009428", @@ -19379,6 +19413,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pgen.1009428; html:https://europepmc.org/articles/PMC8031124; pdf:https://europepmc.org/articles/PMC8031124?pdf=render" }, + { + "id": "36722341", + "doi": "https://doi.org/10.1093/cei/uxad008", + "title": "Practical challenges for functional validation of STAT1 gain of function genetic variants.", + "authorString": "Albuquerque AS, Maimaris J, McKenna AJ, Lambourne J, Moreira F, Workman S, Megy K, Simeoni I, Lango Allen H, NIHR BioResource-Rare Disease Consortium, Morris EC, Burns SO.", + "authorAffiliations": "", + "journalTitle": "Clinical and experimental immunology", + "pubYear": "2023", + "date": "2023-04-01", + "isOpenAccess": "Y", + "keywords": "Flow cytometry; STAT1; Primary Immunodeficiency; Gain Of Function; Chronic Mucocutaneous Candidiasis; Variants Of Unknown Significance", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/cei/uxad008; html:https://europepmc.org/articles/PMC10128160; pdf:https://europepmc.org/articles/PMC10128160?pdf=render" + }, { "id": "32856398", "doi": "https://doi.org/10.1111/1742-6723.13604", @@ -19447,23 +19498,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fcvm.2023.1136764; html:https://europepmc.org/articles/PMC10167048; pdf:https://europepmc.org/articles/PMC10167048?pdf=render" }, - { - "id": "35743743", - "doi": "https://doi.org/10.3390/jpm12060958", - "title": "Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.", - "authorString": "Vo DHT, McGleave G, Overton IM.", - "authorAffiliations": "", - "journalTitle": "Journal of personalized medicine", - "pubYear": "2022", - "date": "2022-06-11", - "isOpenAccess": "Y", - "keywords": "Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render" - }, { "id": "34378227", "doi": "https://doi.org/10.1111/tri.14010", @@ -19482,21 +19516,21 @@ "urls": "doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?pdf=render" }, { - "id": "34734970", - "doi": "https://doi.org/10.1001/jamaophthalmol.2021.4601", - "title": "Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.", - "authorString": "Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).", + "id": "35743743", + "doi": "https://doi.org/10.3390/jpm12060958", + "title": "Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.", + "authorString": "Vo DHT, McGleave G, Overton IM.", "authorAffiliations": "", - "journalTitle": "JAMA ophthalmology", - "pubYear": "2021", - "date": "2021-12-01", + "journalTitle": "Journal of personalized medicine", + "pubYear": "2022", + "date": "2022-06-11", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Importance

Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.

Objective

To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.

Design, setting, participants

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P\u2009<\u20095\u2009\u00d7\u200910-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16\u202f144 individuals with AMD and 17\u202f832 control individuals. Data were analyzed from July 2020 to September 2021.

Exposures

Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.

Main outcomes and measures

Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

Results

A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P\u2009<\u2009.001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P\u2009=\u2009.003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P\u2009=\u2009.004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P\u2009=\u2009.001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Conclusions and relevance

This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.", + "abstract": "The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.", "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599" + "urls": "doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render" }, { "id": "30183734", @@ -19515,6 +19549,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render" }, + { + "id": "34734970", + "doi": "https://doi.org/10.1001/jamaophthalmol.2021.4601", + "title": "Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.", + "authorString": "Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).", + "authorAffiliations": "", + "journalTitle": "JAMA ophthalmology", + "pubYear": "2021", + "date": "2021-12-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.

Objective

To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.

Design, setting, participants

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P\u2009<\u20095\u2009\u00d7\u200910-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16\u202f144 individuals with AMD and 17\u202f832 control individuals. Data were analyzed from July 2020 to September 2021.

Exposures

Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.

Main outcomes and measures

Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

Results

A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P\u2009<\u2009.001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P\u2009=\u2009.003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P\u2009=\u2009.004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P\u2009=\u2009.001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Conclusions and relevance

This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599" + }, { "id": "36689332", "doi": "https://doi.org/10.1093/neuonc/noad021", @@ -19668,6 +19719,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/ans.16426" }, + { + "id": "34761838", + "doi": "https://doi.org/10.1002/biof.1801", + "title": "Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study.", + "authorString": "Mannarino MR, Bianconi V, Gigante B, Strawbridge RJ, Savonen K, Kurl S, Giral P, Smit A, Eriksson P, Tremoli E, Veglia F, Baldassarre D, Pirro M, IMPROVE study group.", + "authorAffiliations": "", + "journalTitle": "BioFactors (Oxford, England)", + "pubYear": "2022", + "date": "2021-11-11", + "isOpenAccess": "Y", + "keywords": "Lymphocyte; neutrophil; cardiovascular; Carotid; Prospective; Imt; Nlr", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1002/biof.1801; html:https://europepmc.org/articles/PMC9299016; pdf:https://europepmc.org/articles/PMC9299016?pdf=render" + }, { "id": "35297548", "doi": "https://doi.org/10.1002/humu.24369", @@ -19702,23 +19770,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/gigascience/giab083; html:https://europepmc.org/articles/PMC8634578; pdf:https://europepmc.org/articles/PMC8634578?pdf=render" }, - { - "id": "34761838", - "doi": "https://doi.org/10.1002/biof.1801", - "title": "Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study.", - "authorString": "Mannarino MR, Bianconi V, Gigante B, Strawbridge RJ, Savonen K, Kurl S, Giral P, Smit A, Eriksson P, Tremoli E, Veglia F, Baldassarre D, Pirro M, IMPROVE study group.", - "authorAffiliations": "", - "journalTitle": "BioFactors (Oxford, England)", - "pubYear": "2022", - "date": "2021-11-11", - "isOpenAccess": "Y", - "keywords": "Lymphocyte; neutrophil; cardiovascular; Carotid; Prospective; Imt; Nlr", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/biof.1801; html:https://europepmc.org/articles/PMC9299016; pdf:https://europepmc.org/articles/PMC9299016?pdf=render" - }, { "id": "34772649", "doi": "https://doi.org/10.1016/s2589-7500(21)00252-1", @@ -19872,23 +19923,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849" }, - { - "id": "34095541", - "doi": "https://doi.org/10.23889/ijpds.v4i2.1134", - "title": "A Profile of the SAIL Databank on the UK Secure Research Platform.", - "authorString": "Jones KH, Ford DV, Thompson S, Lyons RA.", - "authorAffiliations": "", - "journalTitle": "International journal of population data science", - "pubYear": "2019", - "date": "2019-11-20", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.

Approach

SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.

Discussion

Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.

Conclusion

SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.", - "laySummary": "", - "urls": "doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render" - }, { "id": "34127232", "doi": "https://doi.org/10.1016/j.artmed.2021.102083", @@ -19957,6 +19991,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12931-022-02130-6; html:https://europepmc.org/articles/PMC9367123; pdf:https://europepmc.org/articles/PMC9367123?pdf=render" }, + { + "id": "34095541", + "doi": "https://doi.org/10.23889/ijpds.v4i2.1134", + "title": "A Profile of the SAIL Databank on the UK Secure Research Platform.", + "authorString": "Jones KH, Ford DV, Thompson S, Lyons RA.", + "authorAffiliations": "", + "journalTitle": "International journal of population data science", + "pubYear": "2019", + "date": "2019-11-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.

Approach

SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.

Discussion

Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.

Conclusion

SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.", + "laySummary": "", + "urls": "doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render" + }, { "id": "37278928", "doi": "https://doi.org/10.1007/s12265-023-10398-2", @@ -20263,23 +20314,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render" }, - { - "id": "36752447", - "doi": "https://doi.org/10.1016/j.jcmg.2022.11.012", - "title": "Prognostic Value of RV Abnormalities on\u00a0CMR in Patients With Known or Suspected Cardiac Sarcoidosis.", - "authorString": "Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.", - "authorAffiliations": "", - "journalTitle": "JACC. Cardiovascular imaging", - "pubYear": "2023", - "date": "2023-01-11", - "isOpenAccess": "N", - "keywords": "Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95%\u00a0CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 \u00b1 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95%\u00a0CI: 1.7-5.5; P\u00a0< 0.01) for composite events and 3.0 (95%\u00a0CI: 1.3-7.0; P\u00a0< 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95%\u00a0CI: 2.4-9.6]; P\u00a0< 0.01) and a higher risk for SCD (RR: 9.5 [95%\u00a0CI: 4.4-20.5]; P\u00a0< 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95%\u00a0CI: 0.8-0.9), 69% (95%\u00a0CI: 50%-84%), and\u00a090% (95%\u00a0CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.11.012" - }, { "id": "35692035", "doi": "https://doi.org/10.1186/s12916-022-02399-w", @@ -20298,21 +20332,21 @@ "urls": "doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render" }, { - "id": "36228971", - "doi": "https://doi.org/10.1016/j.jclinepi.2022.10.011", - "title": "In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.", - "authorString": "Nichols L, Taverner T, Crowe F, Richardson S, Yau C, Kiddle S, Kirk P, Barrett J, Nirantharakumar K, Griffin S, Edwards D, Marshall T.", + "id": "36752447", + "doi": "https://doi.org/10.1016/j.jcmg.2022.11.012", + "title": "Prognostic Value of RV Abnormalities on\u00a0CMR in Patients With Known or Suspected Cardiac Sarcoidosis.", + "authorString": "Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.", "authorAffiliations": "", - "journalTitle": "Journal of clinical epidemiology", - "pubYear": "2022", - "date": "2022-10-11", - "isOpenAccess": "Y", - "keywords": "Hierarchical cluster analysis; Clustering Methods; Latent Class Analysis; Electronic Medical Records; Multimorbidity; K-means; Multiple Correspondence Analysis", + "journalTitle": "JACC. Cardiovascular imaging", + "pubYear": "2023", + "date": "2023-01-11", + "isOpenAccess": "N", + "keywords": "Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background and objectives

To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering.

Methods

We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples.

Results

In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54).

Conclusion

LCA achieved higher aRI than other clustering algorithms.", + "abstract": "

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95%\u00a0CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 \u00b1 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95%\u00a0CI: 1.7-5.5; P\u00a0< 0.01) for composite events and 3.0 (95%\u00a0CI: 1.3-7.0; P\u00a0< 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95%\u00a0CI: 2.4-9.6]; P\u00a0< 0.01) and a higher risk for SCD (RR: 9.5 [95%\u00a0CI: 4.4-20.5]; P\u00a0< 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95%\u00a0CI: 0.8-0.9), 69% (95%\u00a0CI: 50%-84%), and\u00a090% (95%\u00a0CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.11.012" }, { "id": "31361079", @@ -20331,6 +20365,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/1742-6723.13361" }, + { + "id": "36228971", + "doi": "https://doi.org/10.1016/j.jclinepi.2022.10.011", + "title": "In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.", + "authorString": "Nichols L, Taverner T, Crowe F, Richardson S, Yau C, Kiddle S, Kirk P, Barrett J, Nirantharakumar K, Griffin S, Edwards D, Marshall T.", + "authorAffiliations": "", + "journalTitle": "Journal of clinical epidemiology", + "pubYear": "2022", + "date": "2022-10-11", + "isOpenAccess": "Y", + "keywords": "Hierarchical cluster analysis; Clustering Methods; Latent Class Analysis; Electronic Medical Records; Multimorbidity; K-means; Multiple Correspondence Analysis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and objectives

To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering.

Methods

We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples.

Results

In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54).

Conclusion

LCA achieved higher aRI than other clustering algorithms.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render" + }, { "id": "35351727", "doi": "https://doi.org/10.1136/bmjopen-2021-057909", @@ -20348,23 +20399,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-057909; html:https://europepmc.org/articles/PMC8961119; pdf:https://europepmc.org/articles/PMC8961119?pdf=render" }, - { - "id": "35916366", - "doi": "https://doi.org/10.7554/elife.76272", - "title": "Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.", - "authorString": "Lemmel\u00e4 S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.", - "authorAffiliations": "", - "journalTitle": "eLife", - "pubYear": "2022", - "date": "2022-08-02", - "isOpenAccess": "Y", - "keywords": "Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.", - "laySummary": "", - "urls": "doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render" - }, { "id": "31345952", "doi": "https://doi.org/10.1136/heartjnl-2018-313855", @@ -20382,6 +20416,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/heartjnl-2018-313855" }, + { + "id": "35916366", + "doi": "https://doi.org/10.7554/elife.76272", + "title": "Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.", + "authorString": "Lemmel\u00e4 S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.", + "authorAffiliations": "", + "journalTitle": "eLife", + "pubYear": "2022", + "date": "2022-08-02", + "isOpenAccess": "Y", + "keywords": "Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.", + "laySummary": "", + "urls": "doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render" + }, { "id": "30972781", "doi": "https://doi.org/10.1111/apt.15232", @@ -20688,23 +20739,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/sim.8556; html:https://europepmc.org/articles/PMC8432147; pdf:https://europepmc.org/articles/PMC8432147?pdf=render" }, - { - "id": "35072885", - "doi": "https://doi.org/10.1007/s10439-022-02905-4", - "title": "Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.", - "authorString": "Boonstra MJ, Roudijk RW, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, Loh P, van Dam PM.", - "authorAffiliations": "", - "journalTitle": "Annals of biomedical engineering", - "pubYear": "2022", - "date": "2022-01-24", - "isOpenAccess": "Y", - "keywords": "Electrophysiology; Electrocardiography; Cardiovascular Imaging; Electrocardiographic Imaging; Electro-anatomical Mapping; His-purkinje System; Inverse Electrocardiography; Equivalent Dipole Layer; Non-invasive Cardiac Activation Mapping", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render" - }, { "id": "34769922", "doi": "https://doi.org/10.3390/ijerph182111380", @@ -20722,6 +20756,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph182111380; html:https://europepmc.org/articles/PMC8583338; pdf:https://europepmc.org/articles/PMC8583338?pdf=render" }, + { + "id": "35072885", + "doi": "https://doi.org/10.1007/s10439-022-02905-4", + "title": "Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.", + "authorString": "Boonstra MJ, Roudijk RW, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, Loh P, van Dam PM.", + "authorAffiliations": "", + "journalTitle": "Annals of biomedical engineering", + "pubYear": "2022", + "date": "2022-01-24", + "isOpenAccess": "Y", + "keywords": "Electrophysiology; Electrocardiography; Cardiovascular Imaging; Electrocardiographic Imaging; Electro-anatomical Mapping; His-purkinje System; Inverse Electrocardiography; Equivalent Dipole Layer; Non-invasive Cardiac Activation Mapping", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render" + }, { "id": "33719753", "doi": "https://doi.org/10.1080/13607863.2021.1893270", @@ -20909,23 +20960,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render" }, - { - "id": "36958365", - "doi": "https://doi.org/10.1016/s2352-3018(23)00028-0", - "title": "Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.", - "authorString": "Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.", - "authorAffiliations": "", - "journalTitle": "The lancet. HIV", - "pubYear": "2023", - "date": "2023-03-20", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35\u00b78 years (95% CI 35\u00b72-36\u00b74) of life left if they started ART before 2015, and 39\u00b70 years (38\u00b75-39\u00b75) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34\u00b75 years (33\u00b78-35\u00b72) and 37\u00b70 (36\u00b75-37\u00b76). Women with CD4 counts of fewer than 49 cells per \u03bcL at the start of follow-up had an estimated 19\u00b74 years (18\u00b72-20\u00b75) of life left at age 40 years if they started ART before 2015 and 24\u00b79 years (23\u00b79-25\u00b79) left if they started ART after 2015. The corresponding estimates for men were 18\u00b72 years (17\u00b71-19\u00b74) and 23\u00b77 years (22\u00b77-24\u00b78). Women with CD4 counts of at least 500 cells per \u03bcL at the start of follow-up had an estimated 40\u00b72 years (39\u00b77-40\u00b76) of life left at age 40 years if they started ART before 2015 and 42\u00b70 years (41\u00b77-42\u00b73) left if they started ART after 2015. The corresponding estimates for men were 38\u00b70 years (37\u00b75-38\u00b75) and 39\u00b72 years (38\u00b77-39\u00b77).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0" - }, { "id": "34429368", "doi": "https://doi.org/10.1136/heartjnl-2021-319566", @@ -20943,6 +20977,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/heartjnl-2021-319566" }, + { + "id": "36958365", + "doi": "https://doi.org/10.1016/s2352-3018(23)00028-0", + "title": "Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.", + "authorString": "Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.", + "authorAffiliations": "", + "journalTitle": "The lancet. HIV", + "pubYear": "2023", + "date": "2023-03-20", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35\u00b78 years (95% CI 35\u00b72-36\u00b74) of life left if they started ART before 2015, and 39\u00b70 years (38\u00b75-39\u00b75) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34\u00b75 years (33\u00b78-35\u00b72) and 37\u00b70 (36\u00b75-37\u00b76). Women with CD4 counts of fewer than 49 cells per \u03bcL at the start of follow-up had an estimated 19\u00b74 years (18\u00b72-20\u00b75) of life left at age 40 years if they started ART before 2015 and 24\u00b79 years (23\u00b79-25\u00b79) left if they started ART after 2015. The corresponding estimates for men were 18\u00b72 years (17\u00b71-19\u00b74) and 23\u00b77 years (22\u00b77-24\u00b78). Women with CD4 counts of at least 500 cells per \u03bcL at the start of follow-up had an estimated 40\u00b72 years (39\u00b77-40\u00b76) of life left at age 40 years if they started ART before 2015 and 42\u00b70 years (41\u00b77-42\u00b73) left if they started ART after 2015. The corresponding estimates for men were 38\u00b70 years (37\u00b75-38\u00b75) and 39\u00b72 years (38\u00b77-39\u00b77).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0" + }, { "id": "36944376", "doi": "https://doi.org/10.1098/rsob.220373", @@ -21111,7 +21162,7 @@ "healthCategories": "", "abstract": "

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33\u2009226; 51.3% boys) and pandemic (n=32\u2009446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.", "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render" + "urls": "doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render; pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf" }, { "id": "35410933", @@ -21215,23 +21266,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render" }, - { - "id": "36457326", - "doi": "https://doi.org/10.3389/fpubh.2022.1017337", - "title": "Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.", - "authorString": "Cerbino-Neto J, Peres IT, Varela MC, Brand\u00e3o LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.", - "authorAffiliations": "", - "journalTitle": "Frontiers in public health", - "pubYear": "2022", - "date": "2022-11-14", - "isOpenAccess": "Y", - "keywords": "Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.

Objective

We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.

Methods

We performed a seroepidemiologic survey in all residents of Paquet\u00e1 Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.

Results

We included in the study 3,016 residents of Paquet\u00e1 (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).

Conclusions

Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render" - }, { "id": "32611631", "doi": "https://doi.org/10.1212/wnl.0000000000009814", @@ -21249,6 +21283,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render" }, + { + "id": "36457326", + "doi": "https://doi.org/10.3389/fpubh.2022.1017337", + "title": "Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.", + "authorString": "Cerbino-Neto J, Peres IT, Varela MC, Brand\u00e3o LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.", + "authorAffiliations": "", + "journalTitle": "Frontiers in public health", + "pubYear": "2022", + "date": "2022-11-14", + "isOpenAccess": "Y", + "keywords": "Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.

Objective

We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.

Methods

We performed a seroepidemiologic survey in all residents of Paquet\u00e1 Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.

Results

We included in the study 3,016 residents of Paquet\u00e1 (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).

Conclusions

Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render" + }, { "id": "34606520", "doi": "https://doi.org/10.1371/journal.pmed.1003815", @@ -21453,6 +21504,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/injuryprev-2018-043085" }, + { + "id": "36711167", + "doi": "https://doi.org/10.1093/ehjdh/ztaa016", + "title": "Real-time imputation of missing predictor values in clinical practice.", + "authorString": "Nijman SWJ, Hoogland J, Groenhof TKJ, Brandjes M, Jacobs JJL, Bots ML, Asselbergs FW, Moons KGM, Debray TPA.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Digital health", + "pubYear": "2021", + "date": "2020-12-19", + "isOpenAccess": "Y", + "keywords": "Prediction; Missing Data; Electronic Health Records; Computerized Decision Support System; Real-time Imputation; Joint Modelling Imputation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors, which is not always available in daily practice. We aim to describe two methods for real-time handling of missing predictor values when using prediction models in practice.

Methods and results

We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modelling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance [mean squared error (MSE) of linear predictor], discrimination (c-index), calibration (intercept and slope), and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs. 0.68), and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar.

Conclusions

We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render" + }, { "id": "37339333", "doi": "https://doi.org/10.1002/jia2.26104", @@ -21487,23 +21555,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijcard.2023.05.024" }, - { - "id": "36711167", - "doi": "https://doi.org/10.1093/ehjdh/ztaa016", - "title": "Real-time imputation of missing predictor values in clinical practice.", - "authorString": "Nijman SWJ, Hoogland J, Groenhof TKJ, Brandjes M, Jacobs JJL, Bots ML, Asselbergs FW, Moons KGM, Debray TPA.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Digital health", - "pubYear": "2021", - "date": "2020-12-19", - "isOpenAccess": "Y", - "keywords": "Prediction; Missing Data; Electronic Health Records; Computerized Decision Support System; Real-time Imputation; Joint Modelling Imputation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors, which is not always available in daily practice. We aim to describe two methods for real-time handling of missing predictor values when using prediction models in practice.

Methods and results

We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modelling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance [mean squared error (MSE) of linear predictor], discrimination (c-index), calibration (intercept and slope), and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs. 0.68), and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar.

Conclusions

We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render" - }, { "id": "31711543", "doi": "https://doi.org/10.1186/s13326-019-0214-4", @@ -21589,23 +21640,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?pdf=render" }, - { - "id": "36823471", - "doi": "https://doi.org/10.1038/s42255-023-00753-7", - "title": "Proteogenomic links to human metabolic diseases.", - "authorString": "Koprulu M, Carrasco-Zanini J, Wheeler E, Lockhart S, Kerrison ND, Wareham NJ, Pietzner M, Langenberg C.", - "authorAffiliations": "", - "journalTitle": "Nature metabolism", - "pubYear": "2023", - "date": "2023-02-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 256 unreported protein quantitative trait loci (pQTL); (2) demonstrate shared genetic regulation of 224 cis-pQTLs with 575 specific health outcomes, revealing examples for notable metabolic diseases (such as gastrin-releasing peptide as a potential therapeutic target for type 2 diabetes); (3) improve causal gene assignment at 40% (n\u2009=\u2009192) of overlapping risk loci; and (4) observe convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for 12 proteins, such as TIMD4 for lipoprotein metabolism. Our findings demonstrate the value of integrating complementary proteomic technologies with genomics even at moderate scale to identify new mediators of metabolic diseases with the potential for therapeutic interventions.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s42255-023-00753-7; html:https://europepmc.org/articles/PMC7614946; pdf:https://europepmc.org/articles/PMC7614946?pdf=render" - }, { "id": "34753797", "doi": "https://doi.org/10.2337/db21-0320", @@ -21657,6 +21691,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z" }, + { + "id": "36823471", + "doi": "https://doi.org/10.1038/s42255-023-00753-7", + "title": "Proteogenomic links to human metabolic diseases.", + "authorString": "Koprulu M, Carrasco-Zanini J, Wheeler E, Lockhart S, Kerrison ND, Wareham NJ, Pietzner M, Langenberg C.", + "authorAffiliations": "", + "journalTitle": "Nature metabolism", + "pubYear": "2023", + "date": "2023-02-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 256 unreported protein quantitative trait loci (pQTL); (2) demonstrate shared genetic regulation of 224 cis-pQTLs with 575 specific health outcomes, revealing examples for notable metabolic diseases (such as gastrin-releasing peptide as a potential therapeutic target for type 2 diabetes); (3) improve causal gene assignment at 40% (n\u2009=\u2009192) of overlapping risk loci; and (4) observe convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for 12 proteins, such as TIMD4 for lipoprotein metabolism. Our findings demonstrate the value of integrating complementary proteomic technologies with genomics even at moderate scale to identify new mediators of metabolic diseases with the potential for therapeutic interventions.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s42255-023-00753-7; html:https://europepmc.org/articles/PMC7614946; pdf:https://europepmc.org/articles/PMC7614946?pdf=render" + }, { "id": "PMC8718341", "doi": "https://doi.org/", @@ -21708,23 +21759,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render" }, - { - "id": "37494011", - "doi": "https://doi.org/10.1001/jamacardio.2023.2167", - "title": "Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.", - "authorString": "Aung N, Wang Q, van Duijvenboden S, Burns R, Stoma S, Raisi-Estabragh Z, Ahmet S, Allara E, Wood A, Di Angelantonio E, Danesh J, Munroe PB, Young A, Harvey NC, Codd V, Nelson CP, Petersen SE, Samani NJ.", - "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2023", - "date": "2023-07-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective

To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants

This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure

LTL.

Main outcomes and measures

Cardiovascular imaging traits and HF.

Results

Of 40\u202f459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P\u2009=\u20091.8\u2009\u00d7\u200910-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance

In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756; pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf" - }, { "id": "32709646", "doi": "https://doi.org/10.1136/bmjopen-2019-036099", @@ -21743,21 +21777,21 @@ "urls": "doi:https://doi.org/10.1136/bmjopen-2019-036099; html:https://europepmc.org/articles/PMC7380838; pdf:https://europepmc.org/articles/PMC7380838?pdf=render" }, { - "id": "36764723", - "doi": "https://doi.org/10.1136/bmjopen-2022-067254", - "title": "Associations of remote mental healthcare with clinical outcomes: a natural language processing enriched electronic health record data study protocol.", - "authorString": "Ahmed MS, Kornblum D, Oliver D, Fusar-Poli P, Patel R.", + "id": "37494011", + "doi": "https://doi.org/10.1001/jamacardio.2023.2167", + "title": "Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.", + "authorString": "Aung N, Wang Q, van Duijvenboden S, Burns R, Stoma S, Raisi-Estabragh Z, Ahmet S, Allara E, Wood A, Di Angelantonio E, Danesh J, Munroe PB, Young A, Harvey NC, Codd V, Nelson CP, Petersen SE, Samani NJ.", "authorAffiliations": "", - "journalTitle": "BMJ open", + "journalTitle": "JAMA cardiology", "pubYear": "2023", - "date": "2023-02-10", + "date": "2023-07-26", "isOpenAccess": "Y", - "keywords": "Psychiatry; epidemiology; Telemedicine; Health Informatics", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Introduction

People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.

Methods and analysis

Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80\u2009000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5\u2009million documents to analyse the variation in content of remote versus in-person assessments.

Ethics and dissemination

The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.", + "abstract": "

Importance

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective

To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants

This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure

LTL.

Main outcomes and measures

Cardiovascular imaging traits and HF.

Results

Of 40\u202f459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P\u2009=\u20091.8\u2009\u00d7\u200910-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance

In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.", "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render" + "urls": "doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756; pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf" }, { "id": "33206055", @@ -21776,6 +21810,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/19650; html:https://europepmc.org/articles/PMC7710444; pdf:https://europepmc.org/articles/PMC7710444?pdf=render" }, + { + "id": "36764723", + "doi": "https://doi.org/10.1136/bmjopen-2022-067254", + "title": "Associations of remote mental healthcare with clinical outcomes: a natural language processing enriched electronic health record data study protocol.", + "authorString": "Ahmed MS, Kornblum D, Oliver D, Fusar-Poli P, Patel R.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-02-10", + "isOpenAccess": "Y", + "keywords": "Psychiatry; epidemiology; Telemedicine; Health Informatics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.

Methods and analysis

Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80\u2009000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5\u2009million documents to analyse the variation in content of remote versus in-person assessments.

Ethics and dissemination

The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render" + }, { "id": "32345651", "doi": "https://doi.org/10.2337/dc19-2116", @@ -21844,23 +21895,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xgen.2021.100086; html:https://europepmc.org/articles/PMC8758502; pdf:https://europepmc.org/articles/PMC8758502?pdf=render" }, - { - "id": "36449515", - "doi": "https://doi.org/10.1371/journal.pcbi.1010726", - "title": "Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.", - "authorString": "Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.", - "authorAffiliations": "", - "journalTitle": "PLoS computational biology", - "pubYear": "2022", - "date": "2022-11-30", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render" - }, { "id": "32017129", "doi": "https://doi.org/10.5694/mja2.50485", @@ -21879,21 +21913,21 @@ "urls": "doi:https://doi.org/10.5694/mja2.50485" }, { - "id": "32234121", - "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256", - "title": "Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.", - "authorString": "Russell TW, Hellewell J, Jarvis CI, van Zandvoort K, Abbott S, Ratnayake R, CMMID COVID-19 working group, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ.", + "id": "36449515", + "doi": "https://doi.org/10.1371/journal.pcbi.1010726", + "title": "Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.", + "authorString": "Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.", "authorAffiliations": "", - "journalTitle": "Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin", - "pubYear": "2020", - "date": "2020-03-01", + "journalTitle": "PLoS computational biology", + "pubYear": "2022", + "date": "2022-11-30", "isOpenAccess": "Y", - "keywords": "Coronavirus; outbreak; Severity; Asymptomatic; Case Fatality Ratio; Cruise Ship; Covid-19; Infection Fatality Ratio", - "nationalPriorities": "COVID-19, Improving Public Health", - "healthCategories": "COVID-19, infection", - "abstract": "Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.", "laySummary": "", - "urls": "doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render; pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance" + "urls": "doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render" }, { "id": "31747863", @@ -21912,6 +21946,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/JAHA.119.012551; html:https://europepmc.org/articles/PMC6912961; pdf:https://europepmc.org/articles/PMC6912961?pdf=render" }, + { + "id": "32234121", + "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256", + "title": "Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.", + "authorString": "Russell TW, Hellewell J, Jarvis CI, van Zandvoort K, Abbott S, Ratnayake R, CMMID COVID-19 working group, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ.", + "authorAffiliations": "", + "journalTitle": "Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin", + "pubYear": "2020", + "date": "2020-03-01", + "isOpenAccess": "Y", + "keywords": "Coronavirus; outbreak; Severity; Asymptomatic; Case Fatality Ratio; Cruise Ship; Covid-19; Infection Fatality Ratio", + "nationalPriorities": "COVID-19, Improving Public Health", + "healthCategories": "COVID-19, infection", + "abstract": "Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render; pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance" + }, { "id": "31984563", "doi": "https://doi.org/10.1111/jce.14368", @@ -22303,23 +22354,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1308/rcsann.2021.0206; html:https://europepmc.org/articles/PMC9157920; pdf:https://europepmc.org/articles/PMC9157920?pdf=render; doi:https://doi.org/10.1308/rcsann.2021.0206" }, - { - "id": "34931349", - "doi": "https://doi.org/10.1111/bcp.15191", - "title": "Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.", - "authorString": "Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.", - "authorAffiliations": "", - "journalTitle": "British journal of clinical pharmacology", - "pubYear": "2022", - "date": "2022-01-28", - "isOpenAccess": "Y", - "keywords": "IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

Methods

We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.

Results

A 1\u00a0mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1\u00a0mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.

Conclusions

IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render" - }, { "id": "33782427", "doi": "https://doi.org/10.1038/s41598-021-86266-3", @@ -22337,6 +22371,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render" }, + { + "id": "34931349", + "doi": "https://doi.org/10.1111/bcp.15191", + "title": "Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.", + "authorString": "Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.", + "authorAffiliations": "", + "journalTitle": "British journal of clinical pharmacology", + "pubYear": "2022", + "date": "2022-01-28", + "isOpenAccess": "Y", + "keywords": "IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

Methods

We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.

Results

A 1\u00a0mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1\u00a0mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.

Conclusions

IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render" + }, { "id": "33372068", "doi": "https://doi.org/10.1136/bmjopen-2020-038324", @@ -22524,23 +22575,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41588-021-00783-5" }, - { - "id": "36063293", - "doi": "https://doi.org/10.1186/s12348-022-00304-3", - "title": "Evaluating patient-reported outcome measures (PROMs) for clinical trials and clinical practice in adult patients with uveitis or scleritis: a systematic review.", - "authorString": "O'Donovan C, Panthagani J, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston A, Moore D, Braithwaite T.", - "authorAffiliations": "", - "journalTitle": "Journal of ophthalmic inflammation and infection", - "pubYear": "2022", - "date": "2022-09-05", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Patient reported outcome measures (PROMs) capture impact of disease and treatment on quality of life, and have an emerging role in clinical trial outcome measurement. This study included a systematic review and quality appraisal of PROMs developed or validated for use in adults with uveitis or scleritis. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and grey literature sources, to 5 November 2021. We used established quality criteria to grade each PROM instrument in multiple domains from A (high quality) to C (low quality), and assessed content development, validity, reliability and responsiveness. For instruments developed using classic test theory-based psychometric approaches, we assessed acceptability, item targeting and internal consistency. For instruments developed using Item Response Theory (IRT) (e.g. Rasch analysis), we assessed response categories, dimensionality, measurement precision, item fit statistics, differential item functioning and targeting. We identified and appraised four instruments applicable to certain uveitis types, but none for scleritis. Specifically, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ), a 3-part PROM for Birdshot retinochoroiditis (Birdshot Disease & Medication Symptoms Questionnaire [BD&MSQ], the quality of life (QoL) impact of\u00a0Birdshot Chorioretinopathy\u00a0[QoL BCR], and the QoL impact of BCR medication [QoL Meds],\u00a0the Kings Sarcoidosis Questionnaire\u00a0(KSQ), and a PROM for cytomegalovirus retinitis. These instruments had limited coverage for these heterogeneous conditions, with a focus on very rare subtypes. Psychometric appraisal revealed considerable variability between instruments, limited content development, and only one developed using Item Response Theory. In conclusion, there are few validated PROMs for patients with uveitis and none for scleritis, and existing instruments have suboptimal psychometric performance. We articulate why we do not recommend their inclusion as clinical trial outcome measures for drug licensing purposes, and highlight an unmet need for PROMs applicable to uveitis and scleritis.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12348-022-00304-3; html:https://europepmc.org/articles/PMC9443634; pdf:https://europepmc.org/articles/PMC9443634?pdf=render" - }, { "id": "31446403", "doi": "https://doi.org/10.1136/bmjopen-2018-026677", @@ -22558,6 +22592,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render" }, + { + "id": "36063293", + "doi": "https://doi.org/10.1186/s12348-022-00304-3", + "title": "Evaluating patient-reported outcome measures (PROMs) for clinical trials and clinical practice in adult patients with uveitis or scleritis: a systematic review.", + "authorString": "O'Donovan C, Panthagani J, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston A, Moore D, Braithwaite T.", + "authorAffiliations": "", + "journalTitle": "Journal of ophthalmic inflammation and infection", + "pubYear": "2022", + "date": "2022-09-05", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Patient reported outcome measures (PROMs) capture impact of disease and treatment on quality of life, and have an emerging role in clinical trial outcome measurement. This study included a systematic review and quality appraisal of PROMs developed or validated for use in adults with uveitis or scleritis. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and grey literature sources, to 5 November 2021. We used established quality criteria to grade each PROM instrument in multiple domains from A (high quality) to C (low quality), and assessed content development, validity, reliability and responsiveness. For instruments developed using classic test theory-based psychometric approaches, we assessed acceptability, item targeting and internal consistency. For instruments developed using Item Response Theory (IRT) (e.g. Rasch analysis), we assessed response categories, dimensionality, measurement precision, item fit statistics, differential item functioning and targeting. We identified and appraised four instruments applicable to certain uveitis types, but none for scleritis. Specifically, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ), a 3-part PROM for Birdshot retinochoroiditis (Birdshot Disease & Medication Symptoms Questionnaire [BD&MSQ], the quality of life (QoL) impact of\u00a0Birdshot Chorioretinopathy\u00a0[QoL BCR], and the QoL impact of BCR medication [QoL Meds],\u00a0the Kings Sarcoidosis Questionnaire\u00a0(KSQ), and a PROM for cytomegalovirus retinitis. These instruments had limited coverage for these heterogeneous conditions, with a focus on very rare subtypes. Psychometric appraisal revealed considerable variability between instruments, limited content development, and only one developed using Item Response Theory. In conclusion, there are few validated PROMs for patients with uveitis and none for scleritis, and existing instruments have suboptimal psychometric performance. We articulate why we do not recommend their inclusion as clinical trial outcome measures for drug licensing purposes, and highlight an unmet need for PROMs applicable to uveitis and scleritis.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12348-022-00304-3; html:https://europepmc.org/articles/PMC9443634; pdf:https://europepmc.org/articles/PMC9443634?pdf=render" + }, { "id": "31409800", "doi": "https://doi.org/10.1038/s41467-019-11451-y", @@ -22661,21 +22712,21 @@ "urls": "doi:https://doi.org/10.1186/s13326-021-00249-x; html:https://europepmc.org/articles/PMC8383460; pdf:https://europepmc.org/articles/PMC8383460?pdf=render" }, { - "id": "36351458", - "doi": "https://doi.org/10.1016/s0140-6736(22)02074-8", - "title": "Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.", - "authorString": "Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.", + "id": "31479767", + "doi": "https://doi.org/10.1016/j.jaip.2019.08.030", + "title": "Atopic Eczema in Adulthood and Risk of Depression and Anxiety: A Population-Based Cohort Study.", + "authorString": "Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, Langan SM.", "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2022", - "date": "2022-11-06", + "journalTitle": "The journal of allergy and clinical immunology. In practice", + "pubYear": "2020", + "date": "2019-08-31", "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", + "keywords": "Depression; Anxiety; Atopic Eczema; Atopic Dermatitis; Severity; Population-based", + "nationalPriorities": "Understanding the Causes of Disease", "healthCategories": "", - "abstract": "

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age \u226518 years), large (\u2265500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained \u226550% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90\u2009413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90\u2009409 participants (74\u2009804 [82\u00b77%] participants with diabetes [>99% with type 2 diabetes] and 15\u2009605 [17\u00b73%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1\u00b773 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0\u00b763, 95% CI 0\u00b758-0\u00b769) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0\u00b777, 0\u00b770-0\u00b784) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0\u00b777, 0\u00b774-0\u00b781), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0\u00b786, 0\u00b781-0\u00b792) but did not significantly reduce the risk of non-cardiovascular death (0\u00b794, 0\u00b788-1\u00b702). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.", + "abstract": "

Background

Atopic eczema is a common and debilitating condition associated with depression and anxiety, but the nature of this association remains unclear.

Objective

To explore the temporal relationship between atopic eczema and new depression/anxiety.

Methods

This matched cohort study used routinely collected data from the UK Clinical Practice Research Datalink, linked to hospital admissions data. We identified adults with atopic eczema (1998-2016) using a validated algorithm, and up to 5 individuals without atopic eczema matched on date of diagnosis, age, sex, and general practice. We estimated the hazard ratio (HR) for new depression/anxiety using stratified Cox regression to account for age, sex, calendar period, Index of Multiple Deprivation, glucocorticoid treatment, obesity, smoking, and harmful alcohol use.

Results

We identified 526,808 adults with atopic eczema who were matched to 2,569,030 without. Atopic eczema was associated with increased incidence of new depression (HR, 1.14; 99% CI, 1.12-1.16) and anxiety (HR, 1.17; 99% CI, 1.14-1.19). We observed a stronger effect of atopic eczema on depression with increasing atopic eczema severity (HR [99% CI] compared with no atopic eczema: mild, 1.10 [1.08-1.13]; moderate, 1.19 [1.15-1.23]; and severe, 1.26 [1.17-1.37]). A dose-response association, however, was less apparent for new anxiety diagnosis (HR [99% CI] compared with no atopic eczema: mild, 1.14 [1.11-1.18]; moderate, 1.21 [1.17-1.26]; and severe, 1.15; [1.05-1.25]).

Conclusions

Adults with atopic eczema are more likely to develop new depression and anxiety. For depression, we observed a dose-response relationship with atopic eczema severity.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836" + "urls": "doi:https://doi.org/10.1016/j.jaip.2019.08.030; html:https://europepmc.org/articles/PMC6947493; pdf:https://europepmc.org/articles/PMC6947493?pdf=render" }, { "id": "33559289", @@ -22695,21 +22746,21 @@ "urls": "doi:https://doi.org/10.1002/ejp.1750; pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750" }, { - "id": "31479767", - "doi": "https://doi.org/10.1016/j.jaip.2019.08.030", - "title": "Atopic Eczema in Adulthood and Risk of Depression and Anxiety: A Population-Based Cohort Study.", - "authorString": "Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, Langan SM.", + "id": "36351458", + "doi": "https://doi.org/10.1016/s0140-6736(22)02074-8", + "title": "Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.", + "authorString": "Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.", "authorAffiliations": "", - "journalTitle": "The journal of allergy and clinical immunology. In practice", - "pubYear": "2020", - "date": "2019-08-31", + "journalTitle": "Lancet (London, England)", + "pubYear": "2022", + "date": "2022-11-06", "isOpenAccess": "Y", - "keywords": "Depression; Anxiety; Atopic Eczema; Atopic Dermatitis; Severity; Population-based", - "nationalPriorities": "Understanding the Causes of Disease", + "keywords": "", + "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Atopic eczema is a common and debilitating condition associated with depression and anxiety, but the nature of this association remains unclear.

Objective

To explore the temporal relationship between atopic eczema and new depression/anxiety.

Methods

This matched cohort study used routinely collected data from the UK Clinical Practice Research Datalink, linked to hospital admissions data. We identified adults with atopic eczema (1998-2016) using a validated algorithm, and up to 5 individuals without atopic eczema matched on date of diagnosis, age, sex, and general practice. We estimated the hazard ratio (HR) for new depression/anxiety using stratified Cox regression to account for age, sex, calendar period, Index of Multiple Deprivation, glucocorticoid treatment, obesity, smoking, and harmful alcohol use.

Results

We identified 526,808 adults with atopic eczema who were matched to 2,569,030 without. Atopic eczema was associated with increased incidence of new depression (HR, 1.14; 99% CI, 1.12-1.16) and anxiety (HR, 1.17; 99% CI, 1.14-1.19). We observed a stronger effect of atopic eczema on depression with increasing atopic eczema severity (HR [99% CI] compared with no atopic eczema: mild, 1.10 [1.08-1.13]; moderate, 1.19 [1.15-1.23]; and severe, 1.26 [1.17-1.37]). A dose-response association, however, was less apparent for new anxiety diagnosis (HR [99% CI] compared with no atopic eczema: mild, 1.14 [1.11-1.18]; moderate, 1.21 [1.17-1.26]; and severe, 1.15; [1.05-1.25]).

Conclusions

Adults with atopic eczema are more likely to develop new depression and anxiety. For depression, we observed a dose-response relationship with atopic eczema severity.", + "abstract": "

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age \u226518 years), large (\u2265500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained \u226550% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90\u2009413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90\u2009409 participants (74\u2009804 [82\u00b77%] participants with diabetes [>99% with type 2 diabetes] and 15\u2009605 [17\u00b73%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1\u00b773 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0\u00b763, 95% CI 0\u00b758-0\u00b769) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0\u00b777, 0\u00b770-0\u00b784) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0\u00b777, 0\u00b774-0\u00b781), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0\u00b786, 0\u00b781-0\u00b792) but did not significantly reduce the risk of non-cardiovascular death (0\u00b794, 0\u00b788-1\u00b702). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jaip.2019.08.030; html:https://europepmc.org/articles/PMC6947493; pdf:https://europepmc.org/articles/PMC6947493?pdf=render" + "urls": "doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836; html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836" }, { "id": "32400358", @@ -22728,23 +22779,6 @@ "laySummary": "The authors of this paper estimate the number of cases and spread of COVID-19 using data on critical care admissions within the UK, from a period of February to March 2020. Their results suggest that the UK had hundreds of thousands of COVID-19 cases by the time the national lockdown was implemented. They highlight the usefulness of surveilling critical care data to better understand the dynamics of the epidemic and better inform the response measures.", "urls": "doi:https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000632; html:https://europepmc.org/articles/PMC7219029; pdf:https://europepmc.org/articles/PMC7219029?pdf=render" }, - { - "id": "35967893", - "doi": "https://doi.org/10.1080/20008066.2022.2105577", - "title": "Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.", - "authorString": "Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "European journal of psychotraumatology", - "pubYear": "2022", - "date": "2022-08-09", - "isOpenAccess": "Y", - "keywords": "Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render" - }, { "id": "33591566", "doi": "https://doi.org/10.1007/s43441-021-00263-2", @@ -22762,6 +22796,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1007/s43441-021-00263-2; html:https://europepmc.org/articles/PMC7885762; pdf:https://europepmc.org/articles/PMC7885762?pdf=render" }, + { + "id": "35967893", + "doi": "https://doi.org/10.1080/20008066.2022.2105577", + "title": "Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.", + "authorString": "Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "European journal of psychotraumatology", + "pubYear": "2022", + "date": "2022-08-09", + "isOpenAccess": "Y", + "keywords": "Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render" + }, { "id": "31282950", "doi": "https://doi.org/10.1001/jamaneurol.2019.1812", @@ -22864,23 +22915,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2020.100469; html:https://europepmc.org/articles/PMC7385442; pdf:https://europepmc.org/articles/PMC7385442?pdf=render" }, - { - "id": "37474660", - "doi": "https://doi.org/10.1038/s41591-023-02445-x", - "title": "Considerations for patient and public involvement and engagement in health research.", - "authorString": "Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2023", - "date": "2023-07-20", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41591-023-02445-x" - }, { "id": "33615277", "doi": "https://doi.org/10.1016/j.xpro.2021.100334", @@ -22898,6 +22932,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xpro.2021.100334; html:https://europepmc.org/articles/PMC7881265; pdf:https://europepmc.org/articles/PMC7881265?pdf=render" }, + { + "id": "37474660", + "doi": "https://doi.org/10.1038/s41591-023-02445-x", + "title": "Considerations for patient and public involvement and engagement in health research.", + "authorString": "Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2023", + "date": "2023-07-20", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41591-023-02445-x" + }, { "id": "36545235", "doi": "https://doi.org/10.1177/26335565221145493", @@ -23051,23 +23102,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2352-3026(20)30228-3" }, - { - "id": "36093379", - "doi": "https://doi.org/10.1016/j.isci.2022.105079", - "title": "Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.", - "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.", - "authorAffiliations": "", - "journalTitle": "iScience", - "pubYear": "2022", - "date": "2022-09-05", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Virology; Machine Learning; Health Sciences", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render" - }, { "id": "35641524", "doi": "https://doi.org/10.1038/s41533-022-00280-0", @@ -23085,6 +23119,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41533-022-00280-0; html:https://europepmc.org/articles/PMC9156666; pdf:https://europepmc.org/articles/PMC9156666?pdf=render" }, + { + "id": "36093379", + "doi": "https://doi.org/10.1016/j.isci.2022.105079", + "title": "Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.", + "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.", + "authorAffiliations": "", + "journalTitle": "iScience", + "pubYear": "2022", + "date": "2022-09-05", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Virology; Machine Learning; Health Sciences", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render" + }, { "id": "33837377", "doi": "https://doi.org/10.1038/s41591-021-01310-z", @@ -23102,23 +23153,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41591-021-01310-z; html:https://europepmc.org/articles/PMC7612986; pdf:https://europepmc.org/articles/PMC7612986?pdf=render; pdf:https://www.nature.com/articles/s41591-021-01310-z.pdf" }, - { - "id": "37578823", - "doi": "https://doi.org/10.2196/45233", - "title": "Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.", - "authorString": "Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.", - "authorAffiliations": "", - "journalTitle": "Journal of medical Internet research", - "pubYear": "2023", - "date": "2023-08-14", - "isOpenAccess": "N", - "keywords": "Depression; Mobile phone; Missing Data; Smartphones; Mobile Health; Wearable Devices; Behavioral Patterns; Digital Phenotypes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2196/45233; pdf:https://www.jmir.org/2023/1/e45233/PDF" - }, { "id": "32570434", "doi": "https://doi.org/10.3233/shti200210", @@ -23289,6 +23323,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render" }, + { + "id": "35869125", + "doi": "https://doi.org/10.1038/s41598-022-16375-0", + "title": "Minimising multi-centre radiomics variability through image normalisation: a pilot study.", + "authorString": "Campello VM, Mart\u00edn-Isla C, Izquierdo C, Guala A, Palomares JFR, Vilad\u00e9s D, Descalzo ML, Karakas M, \u00c7avu\u015f E, Raisi-Estabragh Z, Petersen SE, Escalera S, Segu\u00ed S, Lekadir K.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2022", + "date": "2022-07-22", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n\u00a0=\u00a0112) and hypertrophic cardiomyopathy (n\u00a0=\u00a0106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78\u00a0\u00b1\u00a00.08 and 0.79\u00a0\u00b1\u00a00.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45\u00a0\u00b1\u00a00.28 and 0.60\u00a0\u00b1\u00a00.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?pdf=render; pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf" + }, { "id": "37391266", "doi": "https://doi.org/10.1016/s2589-7500(23)00087-0", @@ -23323,23 +23374,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render" }, - { - "id": "35869125", - "doi": "https://doi.org/10.1038/s41598-022-16375-0", - "title": "Minimising multi-centre radiomics variability through image normalisation: a pilot study.", - "authorString": "Campello VM, Mart\u00edn-Isla C, Izquierdo C, Guala A, Palomares JFR, Vilad\u00e9s D, Descalzo ML, Karakas M, \u00c7avu\u015f E, Raisi-Estabragh Z, Petersen SE, Escalera S, Segu\u00ed S, Lekadir K.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2022", - "date": "2022-07-22", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n\u00a0=\u00a0112) and hypertrophic cardiomyopathy (n\u00a0=\u00a0106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78\u00a0\u00b1\u00a00.08 and 0.79\u00a0\u00b1\u00a00.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45\u00a0\u00b1\u00a00.28 and 0.60\u00a0\u00b1\u00a00.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?pdf=render; pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf" - }, { "id": "32023934", "doi": "https://doi.org/10.3390/ijerph17030892", @@ -23544,6 +23578,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render" }, + { + "id": "32393804", + "doi": "https://doi.org/10.1038/s41591-020-0916-2", + "title": "Real-time tracking of self-reported symptoms to predict potential COVID-19.", + "authorString": "Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2020", + "date": "2020-05-11", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio\u2009=\u20096.74; 95% confidence interval\u2009=\u20096.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2; pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf" + }, { "id": "34930919", "doi": "https://doi.org/10.1038/s41467-021-26280-1", @@ -23578,23 +23629,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41591-022-01736-z; html:https://europepmc.org/articles/PMC9117137; pdf:https://europepmc.org/articles/PMC9117137?pdf=render" }, - { - "id": "32393804", - "doi": "https://doi.org/10.1038/s41591-020-0916-2", - "title": "Real-time tracking of self-reported symptoms to predict potential COVID-19.", - "authorString": "Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2020", - "date": "2020-05-11", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio\u2009=\u20096.74; 95% confidence interval\u2009=\u20096.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2; pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf" - }, { "id": "32639589", "doi": "https://doi.org/10.1111/bcp.14458", @@ -23714,23 +23748,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371" }, - { - "id": "33824163", - "doi": "https://doi.org/10.3399/bjgp20x714161", - "title": "Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.", - "authorString": "Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.", - "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", - "pubYear": "2021", - "date": "2021-05-27", - "isOpenAccess": "Y", - "keywords": "Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim

To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design and setting

Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method

Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results

A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion

This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render; pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf" - }, { "id": "31965568", "doi": "https://doi.org/10.1002/bjs.11433", @@ -23748,6 +23765,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/bjs.11433" }, + { + "id": "33824163", + "doi": "https://doi.org/10.3399/bjgp20x714161", + "title": "Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.", + "authorString": "Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.", + "authorAffiliations": "", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2021", + "date": "2021-05-27", + "isOpenAccess": "Y", + "keywords": "Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim

To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design and setting

Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method

Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results

A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion

This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render; pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf" + }, { "id": "32200692", "doi": "https://doi.org/10.1080/09602011.2020.1744453", @@ -24173,23 +24207,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-022-06315-3; html:https://europepmc.org/articles/PMC8844403; pdf:https://europepmc.org/articles/PMC8844403?pdf=render" }, - { - "id": "35434685", - "doi": "https://doi.org/10.1016/j.lanepe.2022.100381", - "title": "Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.", - "authorString": "Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.", - "authorAffiliations": "", - "journalTitle": "The Lancet regional health. Europe", - "pubYear": "2022", - "date": "2022-04-11", - "isOpenAccess": "Y", - "keywords": "Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Aefi, Adverse Events Following Immunisation; Mic, Middle Income Country", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n\u00a0=\u00a013 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render" - }, { "id": "30848519", "doi": "https://doi.org/10.1111/dme.13945", @@ -24207,6 +24224,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/dme.13945" }, + { + "id": "35434685", + "doi": "https://doi.org/10.1016/j.lanepe.2022.100381", + "title": "Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.", + "authorString": "Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.", + "authorAffiliations": "", + "journalTitle": "The Lancet regional health. Europe", + "pubYear": "2022", + "date": "2022-04-11", + "isOpenAccess": "Y", + "keywords": "Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Aefi, Adverse Events Following Immunisation; Mic, Middle Income Country", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n\u00a0=\u00a013 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render" + }, { "id": "35241573", "doi": "https://doi.org/10.1136/bmjqs-2020-012108", @@ -24377,23 +24411,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/18185; html:https://europepmc.org/articles/PMC7381072" }, - { - "id": "33306713", - "doi": "https://doi.org/10.1371/journal.pone.0243383", - "title": "Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.", - "authorString": "Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2020", - "date": "2020-12-11", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.

Methods

This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.

Results

After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.

Conclusions

Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render" - }, { "id": "33310109", "doi": "https://doi.org/10.1016/j.ijid.2020.12.006", @@ -24411,6 +24428,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijid.2020.12.006; html:https://europepmc.org/articles/PMC7725132; pdf:https://europepmc.org/articles/PMC7725132?pdf=render" }, + { + "id": "33306713", + "doi": "https://doi.org/10.1371/journal.pone.0243383", + "title": "Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.", + "authorString": "Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2020", + "date": "2020-12-11", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.

Methods

This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.

Results

After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.

Conclusions

Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render" + }, { "id": "32679111", "doi": "https://doi.org/10.1016/s0140-6736(20)31356-8", @@ -24666,23 +24700,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424" }, - { - "id": "37060915", - "doi": "https://doi.org/10.1016/s0140-6736(23)00510-x", - "title": "Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.", - "authorString": "RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2023", - "date": "2023-04-13", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods

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

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1\u00b759 [95% CI 1\u00b720-2\u00b710]; p=0\u00b70012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3\u00b77% [95% CI 0\u00b77-6\u00b76]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7\u00b74% [95% CI 3\u00b72-11\u00b75]).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render" - }, { "id": "34226637", "doi": "https://doi.org/10.1038/s41366-021-00896-1", @@ -24700,6 +24717,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41366-021-00896-1; html:https://europepmc.org/articles/PMC8455324; pdf:https://europepmc.org/articles/PMC8455324?pdf=render" }, + { + "id": "37060915", + "doi": "https://doi.org/10.1016/s0140-6736(23)00510-x", + "title": "Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.", + "authorString": "RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2023", + "date": "2023-04-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

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

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1\u00b759 [95% CI 1\u00b720-2\u00b710]; p=0\u00b70012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3\u00b77% [95% CI 0\u00b77-6\u00b76]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7\u00b74% [95% CI 3\u00b72-11\u00b75]).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render" + }, { "id": "32909959", "doi": "https://doi.org/10.1136/bmj.m3164", @@ -24904,23 +24938,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-021-82214-3; html:https://europepmc.org/articles/PMC7862387; pdf:https://europepmc.org/articles/PMC7862387?pdf=render" }, - { - "id": "32781946", - "doi": "https://doi.org/10.1098/rspb.2020.1405", - "title": "Key questions for modelling COVID-19 exit strategies.", - "authorString": "Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.", - "authorAffiliations": "", - "journalTitle": "Proceedings. Biological sciences", - "pubYear": "2020", - "date": "2020-08-12", - "isOpenAccess": "Y", - "keywords": "Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render" - }, { "id": "35184736", "doi": "https://doi.org/10.1186/s12916-022-02271-x", @@ -24939,21 +24956,21 @@ "urls": "doi:https://doi.org/10.1186/s12916-022-02271-x; html:https://europepmc.org/articles/PMC8858706; pdf:https://europepmc.org/articles/PMC8858706?pdf=render" }, { - "id": "32692755", - "doi": "https://doi.org/10.1371/journal.pone.0236193", - "title": "A genetic model of ivabradine recapitulates results from randomized clinical trials.", - "authorString": "Legault MA, Sandoval J, Provost S, Barhdadi A, Lemieux Perreault LP, Shah S, Lumbers RT, de Denus S, Tyl B, Tardif JC, Dub\u00e9 MP.", + "id": "32781946", + "doi": "https://doi.org/10.1098/rspb.2020.1405", + "title": "Key questions for modelling COVID-19 exit strategies.", + "authorString": "Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.", "authorAffiliations": "", - "journalTitle": "PloS one", + "journalTitle": "Proceedings. Biological sciences", "pubYear": "2020", - "date": "2020-07-21", + "date": "2020-08-12", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints.

Methods

We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.

Results

Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 \u00d710-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61).

Conclusion

Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.", + "abstract": "Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.", "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0236193; html:https://europepmc.org/articles/PMC7373274; pdf:https://europepmc.org/articles/PMC7373274?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0236193&type=printable" + "urls": "doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render" }, { "id": "31220083", @@ -24972,6 +24989,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render" }, + { + "id": "32692755", + "doi": "https://doi.org/10.1371/journal.pone.0236193", + "title": "A genetic model of ivabradine recapitulates results from randomized clinical trials.", + "authorString": "Legault MA, Sandoval J, Provost S, Barhdadi A, Lemieux Perreault LP, Shah S, Lumbers RT, de Denus S, Tyl B, Tardif JC, Dub\u00e9 MP.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2020", + "date": "2020-07-21", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints.

Methods

We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.

Results

Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 \u00d710-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61).

Conclusion

Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pone.0236193; html:https://europepmc.org/articles/PMC7373274; pdf:https://europepmc.org/articles/PMC7373274?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0236193&type=printable" + }, { "id": "32807724", "doi": "https://doi.org/10.1016/j.auec.2020.07.007", @@ -25091,23 +25125,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jclinepi.2021.01.003" }, - { - "id": "37542272", - "doi": "https://doi.org/10.1186/s12916-023-02948-x", - "title": "Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.", - "authorString": "Henderson AD, Adesanya E, Mulick A, Matthewman J, Vu N, Davies F, Smith CH, Hayes J, Mansfield KE, Langan SM.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2023", - "date": "2023-08-04", - "isOpenAccess": "Y", - "keywords": "Depression; Anxiety; Skin Disease; Electronic Health Records", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render" - }, { "id": "34903266", "doi": "https://doi.org/10.1186/s13059-021-02561-2", @@ -25125,6 +25142,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s13059-021-02561-2; html:https://europepmc.org/articles/PMC8667531; pdf:https://europepmc.org/articles/PMC8667531?pdf=render" }, + { + "id": "37542272", + "doi": "https://doi.org/10.1186/s12916-023-02948-x", + "title": "Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.", + "authorString": "Henderson AD, Adesanya E, Mulick A, Matthewman J, Vu N, Davies F, Smith CH, Hayes J, Mansfield KE, Langan SM.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2023", + "date": "2023-08-04", + "isOpenAccess": "Y", + "keywords": "Depression; Anxiety; Skin Disease; Electronic Health Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render" + }, { "id": "34345870", "doi": "https://doi.org/10.1016/j.bbih.2021.100286", @@ -25278,23 +25312,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fgene.2022.818574; html:https://europepmc.org/articles/PMC8894758; pdf:https://europepmc.org/articles/PMC8894758?pdf=render" }, - { - "id": "37006331", - "doi": "https://doi.org/10.1093/braincomms/fcad041", - "title": "Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.", - "authorString": "Breedon JR, Marshall CR, Giovannoni G, van Heel DA, Genes & Health Research Team , Dobson R, Jacobs BM.", - "authorAffiliations": "", - "journalTitle": "Brain communications", - "pubYear": "2023", - "date": "2023-02-22", - "isOpenAccess": "Y", - "keywords": "Genetics; Multiple sclerosis; Ethnicity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of \u223c50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of \u223c500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render" - }, { "id": "34062542", "doi": "https://doi.org/10.1159/000517521", @@ -25312,6 +25329,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1159/000517521" }, + { + "id": "37006331", + "doi": "https://doi.org/10.1093/braincomms/fcad041", + "title": "Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.", + "authorString": "Breedon JR, Marshall CR, Giovannoni G, van Heel DA, Genes & Health Research Team , Dobson R, Jacobs BM.", + "authorAffiliations": "", + "journalTitle": "Brain communications", + "pubYear": "2023", + "date": "2023-02-22", + "isOpenAccess": "Y", + "keywords": "Genetics; Multiple sclerosis; Ethnicity", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of \u223c50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of \u223c500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render" + }, { "id": "33453763", "doi": "https://doi.org/10.1016/s2468-1253(21)00005-4", @@ -25618,23 +25652,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render" }, - { - "id": "34632432", - "doi": "https://doi.org/10.1016/s2666-5247(21)00128-2", - "title": "Epidemiology of Mycobacterium abscessus in England: an observational study.", - "authorString": "Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Microbe", - "pubYear": "2021", - "date": "2021-10-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.

Methods

In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).

Findings

2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0\u00b738). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1\u00b714 per 10 years, 95% CI 1\u00b704-1\u00b726), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.

Interpretation

Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.

Funding

The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905" - }, { "id": "31363735", "doi": "https://doi.org/10.1093/hmg/ddz187", @@ -25652,6 +25669,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/hmg/ddz187" }, + { + "id": "34632432", + "doi": "https://doi.org/10.1016/s2666-5247(21)00128-2", + "title": "Epidemiology of Mycobacterium abscessus in England: an observational study.", + "authorString": "Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Microbe", + "pubYear": "2021", + "date": "2021-10-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.

Methods

In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).

Findings

2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0\u00b738). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1\u00b714 per 10 years, 95% CI 1\u00b704-1\u00b726), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.

Interpretation

Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.

Funding

The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905" + }, { "id": "32619549", "doi": "https://doi.org/10.1016/j.cels.2020.05.012", @@ -25669,23 +25703,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033" }, - { - "id": "35751107", - "doi": "https://doi.org/10.1186/s13059-022-02702-1", - "title": "Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.", - "authorString": "Zhang P, Amarasinghe HE, Whalley JP, Tay C, Fang H, Migliorini G, Brown AC, Allcock A, Scozzafava G, Rath P, Davies B, Knight JC.", - "authorAffiliations": "", - "journalTitle": "Genome biology", - "pubYear": "2022", - "date": "2022-06-24", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.

Results

We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NF\u03baB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.

Conclusions

Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13059-022-02702-1; html:https://europepmc.org/articles/PMC9229144; pdf:https://europepmc.org/articles/PMC9229144?pdf=render" - }, { "id": "34661196", "doi": "https://doi.org/10.1093/ehjopen/oeab019", @@ -25703,6 +25720,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render" }, + { + "id": "35751107", + "doi": "https://doi.org/10.1186/s13059-022-02702-1", + "title": "Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.", + "authorString": "Zhang P, Amarasinghe HE, Whalley JP, Tay C, Fang H, Migliorini G, Brown AC, Allcock A, Scozzafava G, Rath P, Davies B, Knight JC.", + "authorAffiliations": "", + "journalTitle": "Genome biology", + "pubYear": "2022", + "date": "2022-06-24", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.

Results

We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NF\u03baB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.

Conclusions

Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13059-022-02702-1; html:https://europepmc.org/articles/PMC9229144; pdf:https://europepmc.org/articles/PMC9229144?pdf=render" + }, { "id": "35913736", "doi": "https://doi.org/10.1093/ehjqcco/qcac045", @@ -25924,23 +25958,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render" }, - { - "id": "35849350", - "doi": "https://doi.org/10.1093/nar/gkac612", - "title": "Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.", - "authorString": "Chen J, Cheng J, Chen X, Inoue M, Liu Y, Song CX.", - "authorAffiliations": "", - "journalTitle": "Nucleic acids research", - "pubYear": "2022", - "date": "2022-10-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2\u00d7\u00a0depth, we discovered a significant proportion of CpG sites that\u00a0were not covered in previous 27.5\u00d7 short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/nar/gkac612; html:https://europepmc.org/articles/PMC9561279; pdf:https://europepmc.org/articles/PMC9561279?pdf=render" - }, { "id": "31234639", "doi": "https://doi.org/10.1161/circulationaha.118.038814", @@ -25958,6 +25975,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/CIRCULATIONAHA.118.038814; html:https://europepmc.org/articles/PMC6687408; pdf:https://europepmc.org/articles/PMC6687408?pdf=render" }, + { + "id": "35849350", + "doi": "https://doi.org/10.1093/nar/gkac612", + "title": "Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.", + "authorString": "Chen J, Cheng J, Chen X, Inoue M, Liu Y, Song CX.", + "authorAffiliations": "", + "journalTitle": "Nucleic acids research", + "pubYear": "2022", + "date": "2022-10-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2\u00d7\u00a0depth, we discovered a significant proportion of CpG sites that\u00a0were not covered in previous 27.5\u00d7 short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/nar/gkac612; html:https://europepmc.org/articles/PMC9561279; pdf:https://europepmc.org/articles/PMC9561279?pdf=render" + }, { "id": "32212911", "doi": "https://doi.org/10.1161/jaha.119.013684", @@ -26179,23 +26213,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pgph.0000843; html:https://europepmc.org/articles/PMC10021875; pdf:https://europepmc.org/articles/PMC10021875?pdf=render" }, - { - "id": "37127670", - "doi": "https://doi.org/10.1038/s41588-023-01379-x", - "title": "Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits.", - "authorString": "Zhang BC, Biddanda A, Gunnarsson \u00c1F, Cooper F, Palamara PF.", - "authorAffiliations": "", - "journalTitle": "Nature genetics", - "pubYear": "2023", - "date": "2023-05-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N\u2009=\u2009134, frequency range 0.0007-0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N\u2009=\u200964). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r\u2009=\u20090.72) underlying sequencing variants enriched (4.8\u00d7) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41588-023-01379-x; html:https://europepmc.org/articles/PMC10181934; pdf:https://europepmc.org/articles/PMC10181934?pdf=render" - }, { "id": "30862657", "doi": "https://doi.org/10.2337/dc18-2004", @@ -26230,6 +26247,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(19)30012-3; html:https://europepmc.org/articles/PMC6798263; pdf:https://europepmc.org/articles/PMC6798263?pdf=render" }, + { + "id": "37127670", + "doi": "https://doi.org/10.1038/s41588-023-01379-x", + "title": "Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits.", + "authorString": "Zhang BC, Biddanda A, Gunnarsson \u00c1F, Cooper F, Palamara PF.", + "authorAffiliations": "", + "journalTitle": "Nature genetics", + "pubYear": "2023", + "date": "2023-05-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N\u2009=\u2009134, frequency range 0.0007-0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N\u2009=\u200964). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r\u2009=\u20090.72) underlying sequencing variants enriched (4.8\u00d7) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41588-023-01379-x; html:https://europepmc.org/articles/PMC10181934; pdf:https://europepmc.org/articles/PMC10181934?pdf=render" + }, { "id": "34053260", "doi": "https://doi.org/10.1098/rstb.2020.0283", @@ -26366,23 +26400,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.5694/mja2.50143" }, - { - "id": "31145509", - "doi": "https://doi.org/10.1002/gepi.22215", - "title": "A comparison of two workflows for regulome and transcriptome-based prioritization of genetic variants associated with myocardial mass.", - "authorString": "Manduchi E, Hemerich D, van Setten J, Tragante V, Harakalova M, Pei J, Williams SM, van der Harst P, Asselbergs FW, Moore JH.", - "authorAffiliations": "", - "journalTitle": "Genetic epidemiology", - "pubYear": "2019", - "date": "2019-05-30", - "isOpenAccess": "N", - "keywords": "Functional genomics; Gwas; left ventricular mass; Snp Preselection", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine-map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215" - }, { "id": "33323251", "doi": "https://doi.org/10.1016/s2589-7500(19)30123-2", @@ -26400,6 +26417,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(19)30123-2; pdf:http://www.thelancet.com/article/S2589750019301232/pdf" }, + { + "id": "31145509", + "doi": "https://doi.org/10.1002/gepi.22215", + "title": "A comparison of two workflows for regulome and transcriptome-based prioritization of genetic variants associated with myocardial mass.", + "authorString": "Manduchi E, Hemerich D, van Setten J, Tragante V, Harakalova M, Pei J, Williams SM, van der Harst P, Asselbergs FW, Moore JH.", + "authorAffiliations": "", + "journalTitle": "Genetic epidemiology", + "pubYear": "2019", + "date": "2019-05-30", + "isOpenAccess": "N", + "keywords": "Functional genomics; Gwas; left ventricular mass; Snp Preselection", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine-map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215" + }, { "id": "31702773", "doi": "https://doi.org/10.1093/bioinformatics/btz796", @@ -26451,23 +26485,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/bjd.19597" }, - { - "id": "35717168", - "doi": "https://doi.org/10.1186/s12879-022-07490-4", - "title": "The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.", - "authorString": "Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.", - "authorAffiliations": "", - "journalTitle": "BMC infectious diseases", - "pubYear": "2022", - "date": "2022-06-18", - "isOpenAccess": "Y", - "keywords": "Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >\u20097\u00a0days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n\u2009=\u200965,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the \"first wave\" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>\u200960%) of hospital-acquired infections.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render" - }, { "id": "33246414", "doi": "https://doi.org/10.1186/s12874-020-01163-z", @@ -26485,6 +26502,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12874-020-01163-z; html:https://europepmc.org/articles/PMC7694355; pdf:https://europepmc.org/articles/PMC7694355?pdf=render" }, + { + "id": "35717168", + "doi": "https://doi.org/10.1186/s12879-022-07490-4", + "title": "The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.", + "authorString": "Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.", + "authorAffiliations": "", + "journalTitle": "BMC infectious diseases", + "pubYear": "2022", + "date": "2022-06-18", + "isOpenAccess": "Y", + "keywords": "Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >\u20097\u00a0days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n\u2009=\u200965,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the \"first wave\" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>\u200960%) of hospital-acquired infections.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render" + }, { "id": "37269091", "doi": "https://doi.org/10.1177/10870547231172763", @@ -26517,24 +26551,7 @@ "healthCategories": "", "abstract": "

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from\u00a045 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged \u226570\u2009years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<\u2009\u00a00.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).", "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render" - }, - { - "id": "37433797", - "doi": "https://doi.org/10.1038/s41467-023-38816-8", - "title": "The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom.", - "authorString": "Brand SPC, Cavallaro M, Cumming F, Turner C, Florence I, Blomquist P, Hilton J, Guzman-Rincon LM, House T, Nokes DJ, Keeling MJ.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-07-11", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-023-38816-8; html:https://europepmc.org/articles/PMC10336136; pdf:https://europepmc.org/articles/PMC10336136?pdf=render" + "urls": "doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render; doi:https://doi.org/10.1186/s12877-021-02673-1" }, { "id": "32294163", @@ -26553,6 +26570,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/europace/euaa039; html:https://europepmc.org/articles/PMC7203633; pdf:https://europepmc.org/articles/PMC7203633?pdf=render" }, + { + "id": "37433797", + "doi": "https://doi.org/10.1038/s41467-023-38816-8", + "title": "The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom.", + "authorString": "Brand SPC, Cavallaro M, Cumming F, Turner C, Florence I, Blomquist P, Hilton J, Guzman-Rincon LM, House T, Nokes DJ, Keeling MJ.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-07-11", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41467-023-38816-8; html:https://europepmc.org/articles/PMC10336136; pdf:https://europepmc.org/articles/PMC10336136?pdf=render" + }, { "id": "33947203", "doi": "https://doi.org/10.1161/circulationaha.120.053033", @@ -26772,7 +26806,7 @@ "healthCategories": "", "abstract": "There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10\u2009\u00b0C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render" + "urls": "doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render; pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf" }, { "id": "31492797", @@ -27148,23 +27182,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12911-022-01842-5; html:https://europepmc.org/articles/PMC9009062; pdf:https://europepmc.org/articles/PMC9009062?pdf=render" }, - { - "id": "37315048", - "doi": "https://doi.org/10.1371/journal.pone.0287091", - "title": "LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.", - "authorString": "Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-06-14", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV \u22650.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render" - }, { "id": "31699727", "doi": "https://doi.org/10.1136/bmjopen-2019-030882", @@ -27182,6 +27199,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2019-030882; html:https://europepmc.org/articles/PMC6858135; pdf:https://europepmc.org/articles/PMC6858135?pdf=render" }, + { + "id": "37315048", + "doi": "https://doi.org/10.1371/journal.pone.0287091", + "title": "LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.", + "authorString": "Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-06-14", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods

Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results

We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV \u22650.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion

The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render; pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable" + }, { "id": "35094586", "doi": "https://doi.org/10.1177/17407745221077691", @@ -27216,23 +27250,6 @@ "laySummary": "This article looks at risk assessment for hospital admission in patients with Chronic Obstructive Pulmonary Disease (COPD), which is a group of lung conditions that make it difficult to empty air out of the lungs. The objective of the risk assessment was to eventually aid in clinical decision making and prioritising healthcare resources.", "urls": "doi:https://doi.org/10.1371/journal.pone.0228940; html:https://europepmc.org/articles/PMC7010290; pdf:https://europepmc.org/articles/PMC7010290?pdf=render" }, - { - "id": "36706770", - "doi": "https://doi.org/10.1016/s2214-109x(23)00007-4", - "title": "Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.", - "authorString": "Global Burden of Disease 2021 Health Financing Collaborator Network.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Global health", - "pubYear": "2023", - "date": "2023-01-24", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9\u00b72 trillion (95% uncertainty interval [UI] 9\u00b71-9\u00b73) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7\u00b73 trillion (95% UI 7\u00b72-7\u00b74) in 2019; 293\u00b77 times the $24\u00b78 billion (95% UI 24\u00b73-25\u00b73) spent by low-income countries in 2019. That same year, $43\u00b71 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1\u00b78 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37\u00b78 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12\u00b72% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252\u00b72% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276; doi:https://doi.org/10.1016/s2214-109x(23)00007-4" - }, { "id": "33888728", "doi": "https://doi.org/10.1038/s41598-021-86331-x", @@ -27250,6 +27267,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-021-86331-x; html:https://europepmc.org/articles/PMC8062687; pdf:https://europepmc.org/articles/PMC8062687?pdf=render" }, + { + "id": "36706770", + "doi": "https://doi.org/10.1016/s2214-109x(23)00007-4", + "title": "Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.", + "authorString": "Global Burden of Disease 2021 Health Financing Collaborator Network.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Global health", + "pubYear": "2023", + "date": "2023-01-24", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9\u00b72 trillion (95% uncertainty interval [UI] 9\u00b71-9\u00b73) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7\u00b73 trillion (95% UI 7\u00b72-7\u00b74) in 2019; 293\u00b77 times the $24\u00b78 billion (95% UI 24\u00b73-25\u00b73) spent by low-income countries in 2019. That same year, $43\u00b71 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1\u00b78 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37\u00b78 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12\u00b72% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252\u00b72% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276; doi:https://doi.org/10.1016/s2214-109x(23)00007-4" + }, { "id": "34767555", "doi": "https://doi.org/10.1371/journal.pmed.1003832", @@ -27284,23 +27318,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.clon.2021.12.017" }, - { - "id": "36401199", - "doi": "https://doi.org/10.1186/s12888-022-04275-6", - "title": "Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.", - "authorString": "Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, H\u00fcbel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.", - "authorAffiliations": "", - "journalTitle": "BMC psychiatry", - "pubYear": "2022", - "date": "2022-11-18", - "isOpenAccess": "Y", - "keywords": "Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n\u2009=\u20092890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR\u2009=\u20091.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR\u2009=\u20090.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR\u2009=\u20090.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR\u2009=\u20091.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render" - }, { "id": "37118290", "doi": "https://doi.org/10.1038/s43587-022-00293-x", @@ -27319,21 +27336,21 @@ "urls": "doi:https://doi.org/10.1038/s43587-022-00293-x; html:https://europepmc.org/articles/PMC10154235; pdf:https://europepmc.org/articles/PMC10154235?pdf=render; pdf:https://www.nature.com/articles/s43587-022-00293-x.pdf" }, { - "id": "33025017", - "doi": "https://doi.org/10.1093/schbul/sbaa126", - "title": "Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.", - "authorString": "Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.", + "id": "36401199", + "doi": "https://doi.org/10.1186/s12888-022-04275-6", + "title": "Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.", + "authorString": "Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, H\u00fcbel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.", "authorAffiliations": "", - "journalTitle": "Schizophrenia bulletin", - "pubYear": "2021", - "date": "2021-03-01", - "isOpenAccess": "N", - "keywords": "Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing", + "journalTitle": "BMC psychiatry", + "pubYear": "2022", + "date": "2022-11-18", + "isOpenAccess": "Y", + "keywords": "Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.

Method

The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.

Results

A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.

Conclusions

Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.", + "abstract": "

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n\u2009=\u20092890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR\u2009=\u20091.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR\u2009=\u20090.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR\u2009=\u20090.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR\u2009=\u20091.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.", "laySummary": "", - "urls": "doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf" + "urls": "doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render" }, { "id": "30082368", @@ -27352,6 +27369,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2018-024755; html:https://europepmc.org/articles/PMC6078268; pdf:https://europepmc.org/articles/PMC6078268?pdf=render" }, + { + "id": "33025017", + "doi": "https://doi.org/10.1093/schbul/sbaa126", + "title": "Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.", + "authorString": "Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.", + "authorAffiliations": "", + "journalTitle": "Schizophrenia bulletin", + "pubYear": "2021", + "date": "2021-03-01", + "isOpenAccess": "N", + "keywords": "Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.

Method

The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.

Results

A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.

Conclusions

Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf" + }, { "id": "31820220", "doi": "https://doi.org/10.1007/s10926-019-09867-w", @@ -27522,23 +27556,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jacep.2021.09.001" }, - { - "id": "34708157", - "doi": "https://doi.org/10.12688/wellcomeopenres.16701.3", - "title": "Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.", - "authorString": "Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2021", - "date": "2021-12-21", - "isOpenAccess": "Y", - "keywords": "Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render" - }, { "id": "31815634", "doi": "https://doi.org/10.1186/s12933-019-0972-4", @@ -27556,6 +27573,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12933-019-0972-4; html:https://europepmc.org/articles/PMC6900858; pdf:https://europepmc.org/articles/PMC6900858?pdf=render" }, + { + "id": "34708157", + "doi": "https://doi.org/10.12688/wellcomeopenres.16701.3", + "title": "Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.", + "authorString": "Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2021", + "date": "2021-12-21", + "isOpenAccess": "Y", + "keywords": "Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render" + }, { "id": "33185016", "doi": "https://doi.org/10.1002/art.41593", @@ -27590,23 +27624,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render" }, - { - "id": "36719157", - "doi": "https://doi.org/10.2215/cjn.05080422", - "title": "Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: A Mendelian Randomization Study.", - "authorString": "Donovan K, Herrington WG, Par\u00e9 G, Pigeyre M, Haynes R, Sardell R, Butterworth AS, Folkersen L, Gustafsson S, Wang Q, Baigent C, M\u00e4larstig A, Holmes MV, Staplin N, \n on behalf of the SCALLOP Consortium\n .", - "authorAffiliations": "", - "journalTitle": "Clinical journal of the American Society of Nephrology : CJASN", - "pubYear": "2023", - "date": "2023-01-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.

Methods

SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).

Results

We identified 34 independent variants for circulating FGF-23, which formed a validated genetic score. There were no associations between genetically predicted FGF-23 and any of the cardiovascular or noncardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities.

Conclusions

Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link.

Podcast

This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2215/CJN.05080422; html:https://europepmc.org/articles/PMC7614195; pdf:https://europepmc.org/articles/PMC7614195?pdf=render; pdf:http://uu.diva-portal.org/smash/get/diva2:1745425/FULLTEXT01" - }, { "id": "31233103", "doi": "https://doi.org/10.1093/bioinformatics/btz469", @@ -27624,6 +27641,23 @@ "laySummary": "Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.", "urls": "doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render" }, + { + "id": "36719157", + "doi": "https://doi.org/10.2215/cjn.05080422", + "title": "Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: A Mendelian Randomization Study.", + "authorString": "Donovan K, Herrington WG, Par\u00e9 G, Pigeyre M, Haynes R, Sardell R, Butterworth AS, Folkersen L, Gustafsson S, Wang Q, Baigent C, M\u00e4larstig A, Holmes MV, Staplin N, \n on behalf of the SCALLOP Consortium\n .", + "authorAffiliations": "", + "journalTitle": "Clinical journal of the American Society of Nephrology : CJASN", + "pubYear": "2023", + "date": "2023-01-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.

Methods

SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).

Results

We identified 34 independent variants for circulating FGF-23, which formed a validated genetic score. There were no associations between genetically predicted FGF-23 and any of the cardiovascular or noncardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities.

Conclusions

Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link.

Podcast

This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2215/CJN.05080422; html:https://europepmc.org/articles/PMC7614195; pdf:https://europepmc.org/articles/PMC7614195?pdf=render; pdf:http://uu.diva-portal.org/smash/get/diva2:1745425/FULLTEXT01" + }, { "id": "33062309", "doi": "https://doi.org/10.1177/2059513120952336", @@ -27658,6 +27692,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.media.2021.102050; html:https://europepmc.org/articles/PMC8850869; pdf:https://europepmc.org/articles/PMC8850869?pdf=render" }, + { + "id": "33325834", + "doi": "https://doi.org/10.2196/23530", + "title": "Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.", + "authorString": "Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.", + "authorAffiliations": "", + "journalTitle": "JMIR medical informatics", + "pubYear": "2020", + "date": "2020-12-16", + "isOpenAccess": "Y", + "keywords": "Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511" + }, { "id": "34310590", "doi": "https://doi.org/10.1371/journal.pcbi.1009098", @@ -27676,21 +27727,21 @@ "urls": "doi:https://doi.org/10.1371/journal.pcbi.1009098; html:https://europepmc.org/articles/PMC8354454; pdf:https://europepmc.org/articles/PMC8354454?pdf=render" }, { - "id": "33325834", - "doi": "https://doi.org/10.2196/23530", - "title": "Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.", - "authorString": "Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.", + "id": "32845538", + "doi": "https://doi.org/10.1634/theoncologist.2020-0572", + "title": "Cancer and Risk of COVID-19 Through a General Community Survey.", + "authorString": "Lee KA, Ma W, Sikavi DR, Drew DA, Nguyen LH, Bowyer RCE, Cardoso MJ, Fall T, Freidin MB, Gomez M, Graham M, Guo CG, Joshi AD, Kwon S, Lo CH, Lochlainn MN, Menni C, Murray B, Mehta R, Song M, Sudre CH, Bataille V, Varsavsky T, Visconti A, Franks PW, Wolf J, Steves CJ, Ourselin S, Spector TD, Chan AT, COPE consortium.", "authorAffiliations": "", - "journalTitle": "JMIR medical informatics", - "pubYear": "2020", - "date": "2020-12-16", + "journalTitle": "The oncologist", + "pubYear": "2021", + "date": "2020-09-07", "isOpenAccess": "Y", - "keywords": "Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.", + "abstract": "Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65\u2009years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.", "laySummary": "", - "urls": "doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511" + "urls": "doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render" }, { "id": "33769566", @@ -27709,23 +27760,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/bph.15459" }, - { - "id": "32845538", - "doi": "https://doi.org/10.1634/theoncologist.2020-0572", - "title": "Cancer and Risk of COVID-19 Through a General Community Survey.", - "authorString": "Lee KA, Ma W, Sikavi DR, Drew DA, Nguyen LH, Bowyer RCE, Cardoso MJ, Fall T, Freidin MB, Gomez M, Graham M, Guo CG, Joshi AD, Kwon S, Lo CH, Lochlainn MN, Menni C, Murray B, Mehta R, Song M, Sudre CH, Bataille V, Varsavsky T, Visconti A, Franks PW, Wolf J, Steves CJ, Ourselin S, Spector TD, Chan AT, COPE consortium.", - "authorAffiliations": "", - "journalTitle": "The oncologist", - "pubYear": "2021", - "date": "2020-09-07", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65\u2009years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render" - }, { "id": "33692554", "doi": "https://doi.org/10.1038/s41586-021-03243-6", @@ -28134,23 +28168,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.cels.2021.05.005; html:https://europepmc.org/articles/PMC8201874; doi:https://doi.org/10.1016/j.cels.2021.05.005" }, - { - "id": "36696816", - "doi": "https://doi.org/10.1016/j.ebiom.2023.104441", - "title": "Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.", - "authorString": "Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.", - "authorAffiliations": "", - "journalTitle": "EBioMedicine", - "pubYear": "2023", - "date": "2023-01-23", - "isOpenAccess": "Y", - "keywords": "Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n\u00a0=\u00a086,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n\u00a0=\u00a0406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p\u00a0<\u00a04.9\u00a0\u00d7\u00a010-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59\u00a0g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27\u00a0g, 95% CI: 9, 46) raise, while leucine (-59\u00a0g, 95% CI:\u00a0-106,\u00a0-11) and phenylalanine (-25\u00a0g, 95% CI:\u00a0-47,\u00a0-4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render" - }, { "id": "31196949", "doi": "https://doi.org/10.1183/13993003.02309-2018", @@ -28168,6 +28185,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1183/13993003.02309-2018; html:https://europepmc.org/articles/PMC6727030; pdf:https://europepmc.org/articles/PMC6727030?pdf=render" }, + { + "id": "36696816", + "doi": "https://doi.org/10.1016/j.ebiom.2023.104441", + "title": "Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.", + "authorString": "Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.", + "authorAffiliations": "", + "journalTitle": "EBioMedicine", + "pubYear": "2023", + "date": "2023-01-23", + "isOpenAccess": "Y", + "keywords": "Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n\u00a0=\u00a086,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n\u00a0=\u00a0406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p\u00a0<\u00a04.9\u00a0\u00d7\u00a010-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59\u00a0g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27\u00a0g, 95% CI: 9, 46) raise, while leucine (-59\u00a0g, 95% CI:\u00a0-106,\u00a0-11) and phenylalanine (-25\u00a0g, 95% CI:\u00a0-47,\u00a0-4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render" + }, { "id": "37253531", "doi": "https://doi.org/10.1136/bmjgh-2022-009997", @@ -28491,23 +28525,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2022.101317; html:https://europepmc.org/articles/PMC8898170; pdf:https://europepmc.org/articles/PMC8898170?pdf=render" }, - { - "id": "35246709", - "doi": "https://doi.org/10.1007/s00127-022-02257-3", - "title": "Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.", - "authorString": "de Freitas DF, Patel I, Kadra-Scalzo G, Pritchard M, Shetty H, Broadbent M, Patel R, Downs J, Segev A, Khondoker M, MacCabe JH, Bhui K, Hayes RD.", - "authorAffiliations": "", - "journalTitle": "Social psychiatry and psychiatric epidemiology", - "pubYear": "2022", - "date": "2022-03-04", - "isOpenAccess": "Y", - "keywords": "Clozapine; Health Inequalities; Benign Ethnic Neutropenia; Asian British; Black British; Refractory Psychosis", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder.

Methods

A retrospective cohort study, using information from 11\u00a0years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use.

Results

Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR\u2009=\u20090.49, 95% CI [0.33, 0.74], p\u2009=\u20090.001; Black Caribbean aOR\u2009=\u20090.64, 95% CI [0.43, 0.93], p\u2009=\u20090.019; Black British aOR\u2009=\u20090.61, 95% CI [0.41, 0.91], p\u2009=\u20090.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine.

Conclusion

Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s00127-022-02257-3; html:https://europepmc.org/articles/PMC9246775; pdf:https://europepmc.org/articles/PMC9246775?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02257-3.pdf" - }, { "id": "34555069", "doi": "https://doi.org/10.1371/journal.pone.0257361", @@ -28525,6 +28542,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pone.0257361; html:https://europepmc.org/articles/PMC8460020; pdf:https://europepmc.org/articles/PMC8460020?pdf=render" }, + { + "id": "35246709", + "doi": "https://doi.org/10.1007/s00127-022-02257-3", + "title": "Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.", + "authorString": "de Freitas DF, Patel I, Kadra-Scalzo G, Pritchard M, Shetty H, Broadbent M, Patel R, Downs J, Segev A, Khondoker M, MacCabe JH, Bhui K, Hayes RD.", + "authorAffiliations": "", + "journalTitle": "Social psychiatry and psychiatric epidemiology", + "pubYear": "2022", + "date": "2022-03-04", + "isOpenAccess": "Y", + "keywords": "Clozapine; Health Inequalities; Benign Ethnic Neutropenia; Asian British; Black British; Refractory Psychosis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder.

Methods

A retrospective cohort study, using information from 11\u00a0years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use.

Results

Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR\u2009=\u20090.49, 95% CI [0.33, 0.74], p\u2009=\u20090.001; Black Caribbean aOR\u2009=\u20090.64, 95% CI [0.43, 0.93], p\u2009=\u20090.019; Black British aOR\u2009=\u20090.61, 95% CI [0.41, 0.91], p\u2009=\u20090.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine.

Conclusion

Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s00127-022-02257-3; html:https://europepmc.org/articles/PMC9246775; pdf:https://europepmc.org/articles/PMC9246775?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02257-3.pdf" + }, { "id": "31101093", "doi": "https://doi.org/10.1186/s12889-019-6888-9", @@ -28642,7 +28676,7 @@ "healthCategories": "", "abstract": "

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30\u2009days of hospitalization.

Results

We studied 133\u2009589 patients diagnosed and 48\u2009418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged \u226550\u2009years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70\u2009660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.", "laySummary": "", - "urls": "doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render" + "urls": "doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render; pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf" }, { "id": "32073627", @@ -28729,23 +28763,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/17003; html:https://europepmc.org/articles/PMC7600019" }, - { - "id": "32835195", - "doi": "https://doi.org/10.1016/s2589-7500(20)30134-5", - "title": "The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.", - "authorString": "Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2020", - "date": "2020-06-12", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render" - }, { "id": "30351417", "doi": "https://doi.org/10.1093/bioinformatics/bty837", @@ -28763,6 +28780,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/bioinformatics/bty837; html:https://europepmc.org/articles/PMC6546129; pdf:https://europepmc.org/articles/PMC6546129?pdf=render" }, + { + "id": "32835195", + "doi": "https://doi.org/10.1016/s2589-7500(20)30134-5", + "title": "The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.", + "authorString": "Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2020", + "date": "2020-06-12", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render" + }, { "id": "37338017", "doi": "https://doi.org/10.1111/jvh.13863", @@ -28899,23 +28933,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41366-020-0642-3; html:https://europepmc.org/articles/PMC7577847; pdf:https://europepmc.org/articles/PMC7577847?pdf=render" }, - { - "id": "35498042", - "doi": "https://doi.org/10.3389/fcvm.2022.768972", - "title": "Unravelling the Difference Between Men and Women in Post-CABG Survival.", - "authorString": "Schmidt AF, Haitjema S, Sartipy U, Holzmann MJ, Malenka DJ, Ross CS, van Gilst W, Rouleau JL, Meeder AM, Baker RA, Shiomi H, Kimura T, Tran L, Smith JA, Reid CM, Asselbergs FW, den Ruijter HM.", - "authorAffiliations": "", - "journalTitle": "Frontiers in cardiovascular medicine", - "pubYear": "2022", - "date": "2022-04-13", - "isOpenAccess": "Y", - "keywords": "Atherosclerosis; Sex; Gender; Prognosis; Cabg; Outcome", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups.

Methods

Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan-Meier estimates, and Cox's proportional hazards model.

Results

During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 \u00d7 10-5, respectively), with an effect reversal in younger women.

Conclusion

Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?pdf=render" - }, { "id": "32135128", "doi": "https://doi.org/10.1016/s2352-3026(20)30031-4", @@ -28933,6 +28950,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2352-3026(20)30031-4" }, + { + "id": "35498042", + "doi": "https://doi.org/10.3389/fcvm.2022.768972", + "title": "Unravelling the Difference Between Men and Women in Post-CABG Survival.", + "authorString": "Schmidt AF, Haitjema S, Sartipy U, Holzmann MJ, Malenka DJ, Ross CS, van Gilst W, Rouleau JL, Meeder AM, Baker RA, Shiomi H, Kimura T, Tran L, Smith JA, Reid CM, Asselbergs FW, den Ruijter HM.", + "authorAffiliations": "", + "journalTitle": "Frontiers in cardiovascular medicine", + "pubYear": "2022", + "date": "2022-04-13", + "isOpenAccess": "Y", + "keywords": "Atherosclerosis; Sex; Gender; Prognosis; Cabg; Outcome", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups.

Methods

Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan-Meier estimates, and Cox's proportional hazards model.

Results

During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 \u00d7 10-5, respectively), with an effect reversal in younger women.

Conclusion

Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?pdf=render" + }, { "id": "34442458", "doi": "https://doi.org/10.3390/jpm11080814", @@ -28967,23 +29001,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?pdf=render; pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf" }, - { - "id": "36647047", - "doi": "https://doi.org/10.1186/s12916-022-02722-5", - "title": "Polypharmacy during pregnancy and\u00a0associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.", - "authorString": "Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2023", - "date": "2023-01-16", - "isOpenAccess": "Y", - "keywords": "Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render" - }, { "id": "32808938", "doi": "https://doi.org/10.2196/17022", @@ -29001,6 +29018,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/17022; html:https://europepmc.org/articles/PMC7463397" }, + { + "id": "36647047", + "doi": "https://doi.org/10.1186/s12916-022-02722-5", + "title": "Polypharmacy during pregnancy and\u00a0associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.", + "authorString": "Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2023", + "date": "2023-01-16", + "isOpenAccess": "Y", + "keywords": "Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render" + }, { "id": "32714939", "doi": "https://doi.org/10.3389/fnut.2020.00080", @@ -29137,23 +29171,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3399/BJGP.2022.0389; html:https://europepmc.org/articles/PMC10170524; pdf:https://europepmc.org/articles/PMC10170524?pdf=render" }, - { - "id": "32303767", - "doi": "https://doi.org/10.1093/schbul/sbaa040", - "title": "Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study. ", - "authorString": "Fusar-Poli P, De Micheli A, Patel R, Signorini L, Miah S, Spencer T, McGuire P.", - "authorAffiliations": "", - "journalTitle": "Schizophrenia bulletin", - "pubYear": "2020", - "date": "2020-04-18", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/schbul/sbaa040; html:https://europepmc.org/articles/PMC7505186; pdf:https://europepmc.org/articles/PMC7505186?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa040; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf" - }, { "id": "29780001", "doi": "https://doi.org/10.1016/s2352-3026(18)30053-x", @@ -29171,6 +29188,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2352-3026(18)30053-X; html:https://europepmc.org/articles/PMC6438177; pdf:https://europepmc.org/articles/PMC6438177?pdf=render; doi:https://doi.org/10.1016/s2352-3026(18)30053-x" }, + { + "id": "32303767", + "doi": "https://doi.org/10.1093/schbul/sbaa040", + "title": "Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study. ", + "authorString": "Fusar-Poli P, De Micheli A, Patel R, Signorini L, Miah S, Spencer T, McGuire P.", + "authorAffiliations": "", + "journalTitle": "Schizophrenia bulletin", + "pubYear": "2020", + "date": "2020-04-18", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/schbul/sbaa040; html:https://europepmc.org/articles/PMC7505186; pdf:https://europepmc.org/articles/PMC7505186?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa040; pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf" + }, { "id": "32247823", "doi": "https://doi.org/10.1016/j.jhep.2020.03.032", @@ -29222,23 +29256,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render" }, - { - "id": "37538507", - "doi": "https://doi.org/10.1016/j.rpth.2023.100175", - "title": "PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.", - "authorString": "Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.", - "authorAffiliations": "", - "journalTitle": "Research and practice in thrombosis and haemostasis", - "pubYear": "2023", - "date": "2023-05-14", - "isOpenAccess": "Y", - "keywords": "Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.

Objectives

To reveal new regulatory genes for platelet count (PLT).

Methods

Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.

Results

Of 1588 significantly associated variants (P\u00a0< 5\u00a0\u00d7 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 \u2265 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K).

Conclusion

Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render" - }, { "id": "34740937", "doi": "https://doi.org/10.1136/bmjopen-2021-056601", @@ -29256,6 +29273,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render" }, + { + "id": "37538507", + "doi": "https://doi.org/10.1016/j.rpth.2023.100175", + "title": "PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.", + "authorString": "Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.", + "authorAffiliations": "", + "journalTitle": "Research and practice in thrombosis and haemostasis", + "pubYear": "2023", + "date": "2023-05-14", + "isOpenAccess": "Y", + "keywords": "Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.

Objectives

To reveal new regulatory genes for platelet count (PLT).

Methods

Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.

Results

Of 1588 significantly associated variants (P\u00a0< 5\u00a0\u00d7 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 \u2265 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K).

Conclusion

Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render" + }, { "id": "34732839", "doi": "https://doi.org/10.1038/s41379-021-00953-0", @@ -29664,23 +29698,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2352-4642(19)30114-2" }, - { - "id": "37247330", - "doi": "https://doi.org/10.1093/eurheartj/ehad260", - "title": "SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.", - "authorString": "SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "Y", - "keywords": "Cardiovascular diseases; Prediction model; Diabetes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render; doi:https://doi.org/10.1093/eurheartj/ehad260" - }, { "id": "31810636", "doi": "https://doi.org/10.1016/j.injury.2019.11.034", @@ -29698,6 +29715,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.injury.2019.11.034" }, + { + "id": "37247330", + "doi": "https://doi.org/10.1093/eurheartj/ehad260", + "title": "SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.", + "authorString": "SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.", + "authorAffiliations": "", + "journalTitle": "European heart journal", + "pubYear": "2023", + "date": "2023-07-01", + "isOpenAccess": "Y", + "keywords": "Cardiovascular diseases; Prediction model; Diabetes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render; doi:https://doi.org/10.1093/eurheartj/ehad260" + }, { "id": "30949070", "doi": "https://doi.org/10.3389/fpsyt.2019.00109", @@ -29749,23 +29783,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render" }, - { - "id": "36244350", - "doi": "https://doi.org/10.1016/s2468-2667(22)00225-0", - "title": "The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.", - "authorString": "European Antimicrobial Resistance Collaborators.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Public health", - "pubYear": "2022", - "date": "2022-10-14", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.

Methods

We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings

We estimated 541\u2008000 deaths (95% UI 370\u2008000-763\u2008000) associated with bacterial AMR and 133\u2008000 deaths (90\u2008100-188\u2008000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195\u2008000 deaths (104\u2008000-333\u2008000) associated with resistance, followed by intra-abdominal infections (127\u2008000 deaths [81\u2008900-185\u2008000]) and respiratory infections (120\u2008000 deaths [94\u2008500-154\u2008000]). Seven leading pathogens were responsible for about 457\u2008000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.

Interpretation

The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253; pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf" - }, { "id": "31358974", "doi": "https://doi.org/10.1038/s41562-019-0653-z", @@ -29783,6 +29800,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z" }, + { + "id": "36244350", + "doi": "https://doi.org/10.1016/s2468-2667(22)00225-0", + "title": "The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.", + "authorString": "European Antimicrobial Resistance Collaborators.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Public health", + "pubYear": "2022", + "date": "2022-10-14", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.

Methods

We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings

We estimated 541\u2008000 deaths (95% UI 370\u2008000-763\u2008000) associated with bacterial AMR and 133\u2008000 deaths (90\u2008100-188\u2008000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195\u2008000 deaths (104\u2008000-333\u2008000) associated with resistance, followed by intra-abdominal infections (127\u2008000 deaths [81\u2008900-185\u2008000]) and respiratory infections (120\u2008000 deaths [94\u2008500-154\u2008000]). Seven leading pathogens were responsible for about 457\u2008000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.

Interpretation

The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253; pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf" + }, { "id": "35322056", "doi": "https://doi.org/10.1038/s41598-022-08351-5", @@ -29817,23 +29851,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render" }, - { - "id": "35948708", - "doi": "https://doi.org/10.1038/s41586-022-05023-2", - "title": "Spatially resolved clonal copy number alterations in benign and malignant tissue.", - "authorString": "Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstr\u00e5hle L, Bergenstr\u00e5hle J, Larsson L, Alonso Galicia L, Shamikh A, Basmaci E, D\u00edaz De St\u00e5hl T, Rajakumar T, Doultsinos D, Thrane K, Ji AL, Khavari PA, Tarish F, Tanoglidi A, Maaskola J, Colling R, Mirtti T, Hamdy FC, Woodcock DJ, Helleday T, Mills IG, Lamb AD, Lundeberg J.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2022", - "date": "2022-08-10", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41586-022-05023-2; html:https://europepmc.org/articles/PMC9365699; pdf:https://europepmc.org/articles/PMC9365699?pdf=render" - }, { "id": "30984759", "doi": "https://doi.org/10.3389/fmed.2019.00048", @@ -29851,6 +29868,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fmed.2019.00048; html:https://europepmc.org/articles/PMC6449432; pdf:https://europepmc.org/articles/PMC6449432?pdf=render" }, + { + "id": "35948708", + "doi": "https://doi.org/10.1038/s41586-022-05023-2", + "title": "Spatially resolved clonal copy number alterations in benign and malignant tissue.", + "authorString": "Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstr\u00e5hle L, Bergenstr\u00e5hle J, Larsson L, Alonso Galicia L, Shamikh A, Basmaci E, D\u00edaz De St\u00e5hl T, Rajakumar T, Doultsinos D, Thrane K, Ji AL, Khavari PA, Tarish F, Tanoglidi A, Maaskola J, Colling R, Mirtti T, Hamdy FC, Woodcock DJ, Helleday T, Mills IG, Lamb AD, Lundeberg J.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2022", + "date": "2022-08-10", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41586-022-05023-2; html:https://europepmc.org/articles/PMC9365699; pdf:https://europepmc.org/articles/PMC9365699?pdf=render" + }, { "id": "33528799", "doi": "https://doi.org/10.1007/s12471-021-01542-1", @@ -29953,23 +29987,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render" }, - { - "id": "37565978", - "doi": "https://doi.org/10.1016/j.jchf.2023.07.007", - "title": "Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.", - "authorString": "Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.", - "authorAffiliations": "", - "journalTitle": "JACC. Heart failure", - "pubYear": "2023", - "date": "2023-08-09", - "isOpenAccess": "N", - "keywords": "Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age\u00a0<12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95%\u00a0CI: 1.15-3.04; P\u00a0=\u00a00.012) and at age\u00a0\u22641 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95%\u00a0CI: 4.81-93.20; P\u00a0< 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95%\u00a0CI: 1.09-5.50; P\u00a0=\u00a00.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95%\u00a0CI: 1.15-2.87; P\u00a0=\u00a00.010) and at age\u00a0\u22645 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95%\u00a0CI:\u00a05.16-291.88; P\u00a0< 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may\u00a0be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at\u00a0<12 years.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jchf.2023.07.007" - }, { "id": "35509371", "doi": "https://doi.org/10.12688/wellcomeopenres.16883.2", @@ -30004,6 +30021,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/genes11040460; html:https://europepmc.org/articles/PMC7230372; pdf:https://europepmc.org/articles/PMC7230372?pdf=render" }, + { + "id": "37565978", + "doi": "https://doi.org/10.1016/j.jchf.2023.07.007", + "title": "Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.", + "authorString": "Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.", + "authorAffiliations": "", + "journalTitle": "JACC. Heart failure", + "pubYear": "2023", + "date": "2023-08-09", + "isOpenAccess": "N", + "keywords": "Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age\u00a0<12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95%\u00a0CI: 1.15-3.04; P\u00a0=\u00a00.012) and at age\u00a0\u22641 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95%\u00a0CI: 4.81-93.20; P\u00a0< 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95%\u00a0CI: 1.09-5.50; P\u00a0=\u00a00.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95%\u00a0CI: 1.15-2.87; P\u00a0=\u00a00.010) and at age\u00a0\u22645 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95%\u00a0CI:\u00a05.16-291.88; P\u00a0< 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may\u00a0be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at\u00a0<12 years.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jchf.2023.07.007" + }, { "id": "33449072", "doi": "https://doi.org/10.1093/gerona/glab009", @@ -30123,23 +30157,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.media.2021.102213" }, - { - "id": "36865374", - "doi": "https://doi.org/10.12688/wellcomeopenres.18175.1", - "title": "GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.", - "authorString": "Hunter RF, Rodgers SE, Hilton J, Clarke M, Garcia L, Ward Thompson C, Geary R, Green MA, O'Neill C, Longo A, Lovell R, Nurse A, Wheeler BW, Clement S, Porroche-Escudero A, Mitchell R, Barr B, Barry J, Bell S, Bryan D, Buchan I, Butters O, Clemens T, Clewley N, Corcoran R, Elliott L, Ellis G, Guell C, Jurek-Loughrey A, Kee F, Maguire A, Maskell S, Murtagh B, Smith G, Taylor T, Jepson R, GroundsWell Consortium.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2022", - "date": "2022-09-20", - "isOpenAccess": "Y", - "keywords": "Public Health; Non-Communicable Disease; Green And Blue Space; Complex Systems; Data Science; Citizen Science; Interdisciplinary; Health Inequalities", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes , with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render" - }, { "id": "34750105", "doi": "https://doi.org/10.3399/bjgp.2021.0380", @@ -30158,21 +30175,21 @@ "urls": "doi:https://doi.org/10.3399/BJGP.2021.0380; html:https://europepmc.org/articles/PMC8589464; pdf:https://europepmc.org/articles/PMC8589464?pdf=render" }, { - "id": "34732073", - "doi": "https://doi.org/10.1161/strokeaha.121.034787", - "title": "Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.", - "authorString": "Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.", + "id": "36865374", + "doi": "https://doi.org/10.12688/wellcomeopenres.18175.1", + "title": "GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.", + "authorString": "Hunter RF, Rodgers SE, Hilton J, Clarke M, Garcia L, Ward Thompson C, Geary R, Green MA, O'Neill C, Longo A, Lovell R, Nurse A, Wheeler BW, Clement S, Porroche-Escudero A, Mitchell R, Barr B, Barry J, Bell S, Bryan D, Buchan I, Butters O, Clemens T, Clewley N, Corcoran R, Elliott L, Ellis G, Guell C, Jurek-Loughrey A, Kee F, Maguire A, Maskell S, Murtagh B, Smith G, Taylor T, Jepson R, GroundsWell Consortium.", "authorAffiliations": "", - "journalTitle": "Stroke", - "pubYear": "2021", - "date": "2021-11-04", + "journalTitle": "Wellcome open research", + "pubYear": "2022", + "date": "2022-09-20", "isOpenAccess": "Y", - "keywords": "Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19", + "keywords": "Public Health; Non-Communicable Disease; Green And Blue Space; Complex Systems; Data Science; Citizen Science; Interdisciplinary; Health Inequalities", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was \u22482%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.", + "abstract": "Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes , with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.", "laySummary": "", - "urls": "doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render" + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render" }, { "id": "31350550", @@ -30191,6 +30208,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/cvr/cvz197" }, + { + "id": "34732073", + "doi": "https://doi.org/10.1161/strokeaha.121.034787", + "title": "Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.", + "authorString": "Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.", + "authorAffiliations": "", + "journalTitle": "Stroke", + "pubYear": "2021", + "date": "2021-11-04", + "isOpenAccess": "Y", + "keywords": "Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was \u22482%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render" + }, { "id": "35545669", "doi": "https://doi.org/10.1038/s41586-022-04712-2", @@ -30208,23 +30242,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41586-022-04712-2; html:https://europepmc.org/articles/PMC9117138; pdf:https://europepmc.org/articles/PMC9117138?pdf=render" }, - { - "id": "34503493", - "doi": "https://doi.org/10.1186/s12916-021-02107-0", - "title": "Estimating the impact of reopening schools on the reproduction number of SARS-CoV-2 in England, using weekly contact survey data.", - "authorString": "Munday JD, Jarvis CI, Gimma A, Wong KLM, van Zandvoort K, CMMID COVID-19 Working Group, Funk S, Edmunds WJ.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2021", - "date": "2021-09-10", - "isOpenAccess": "Y", - "keywords": "School Closure; Reproduction Number; Social Contacts; Covid-19; Sars-cov-2; Comix", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Schools were closed in England on 4 January 2021 as part of increased national restrictions to curb transmission of SARS-CoV-2. The UK government reopened schools on 8 March. Although there was evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings and the resulting impact on the overall transmission rate in the population were not clear.

Methods

We measured social contacts of >\u20095000 participants weekly from March 2020, including periods when schools were both open and closed, amongst other restrictions. We combined these data with estimates of the susceptibility and infectiousness of children compared with adults to estimate the impact of reopening schools on the reproduction number.

Results

Our analysis indicates that reopening all schools under the same measures as previous periods that combined lockdown with face-to-face schooling would be likely to increase the reproduction number substantially. Assuming a baseline of 0.8, we estimated a likely increase to between 1.0 and 1.5 with the reopening of all schools or to between 0.9 and 1.2 reopening primary or secondary schools alone.

Conclusion

Our results suggest that reopening schools would likely halt the fall in cases observed between January and March 2021 and would risk a return to rising infections, but these estimates relied heavily on the latest estimates or reproduction number and the validity of the susceptibility and infectiousness profiles we used at the time of reopening.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-021-02107-0; html:https://europepmc.org/articles/PMC8428960; pdf:https://europepmc.org/articles/PMC8428960?pdf=render" - }, { "id": "31204027", "doi": "https://doi.org/10.1016/j.injury.2019.06.012", @@ -30242,6 +30259,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.injury.2019.06.012" }, + { + "id": "34503493", + "doi": "https://doi.org/10.1186/s12916-021-02107-0", + "title": "Estimating the impact of reopening schools on the reproduction number of SARS-CoV-2 in England, using weekly contact survey data.", + "authorString": "Munday JD, Jarvis CI, Gimma A, Wong KLM, van Zandvoort K, CMMID COVID-19 Working Group, Funk S, Edmunds WJ.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2021", + "date": "2021-09-10", + "isOpenAccess": "Y", + "keywords": "School Closure; Reproduction Number; Social Contacts; Covid-19; Sars-cov-2; Comix", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Schools were closed in England on 4 January 2021 as part of increased national restrictions to curb transmission of SARS-CoV-2. The UK government reopened schools on 8 March. Although there was evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings and the resulting impact on the overall transmission rate in the population were not clear.

Methods

We measured social contacts of >\u20095000 participants weekly from March 2020, including periods when schools were both open and closed, amongst other restrictions. We combined these data with estimates of the susceptibility and infectiousness of children compared with adults to estimate the impact of reopening schools on the reproduction number.

Results

Our analysis indicates that reopening all schools under the same measures as previous periods that combined lockdown with face-to-face schooling would be likely to increase the reproduction number substantially. Assuming a baseline of 0.8, we estimated a likely increase to between 1.0 and 1.5 with the reopening of all schools or to between 0.9 and 1.2 reopening primary or secondary schools alone.

Conclusion

Our results suggest that reopening schools would likely halt the fall in cases observed between January and March 2021 and would risk a return to rising infections, but these estimates relied heavily on the latest estimates or reproduction number and the validity of the susceptibility and infectiousness profiles we used at the time of reopening.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-021-02107-0; html:https://europepmc.org/articles/PMC8428960; pdf:https://europepmc.org/articles/PMC8428960?pdf=render" + }, { "id": "35584845", "doi": "https://doi.org/10.1136/bmj-2022-070904", @@ -30310,23 +30344,6 @@ "laySummary": "Gibson et al.\u2019s study investigates whether having fish in diet will have an effect on urinary metabolism. They\u2019ve assessed dietary and BP measurement across Asian and Westerns and shown that the relationship was stronger in Japanese population compared to Western population and is highly context dependant. ", "urls": "doi:https://doi.org/10.1093/ajcn/nqz293; html:https://europepmc.org/articles/PMC6997096; pdf:https://europepmc.org/articles/PMC6997096?pdf=render" }, - { - "id": "35861824", - "doi": "https://doi.org/10.1161/jaha.121.025935", - "title": "Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.", - "authorString": "Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2022", - "date": "2022-07-13", - "isOpenAccess": "Y", - "keywords": "Biomarkers; Childhood Cancer Survivors; Cardio\u2010oncology; Chemokine Ligands; Anthracycline\u2010related Cardiomyopathy; Cancer Therapy\u2013related Cardiac Dysfunction", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction \u226553% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render" - }, { "id": "31021418", "doi": "https://doi.org/10.1111/bjd.18046", @@ -30344,6 +30361,23 @@ "laySummary": " ", "urls": "doi:https://doi.org/10.1111/bjd.18046; html:https://europepmc.org/articles/PMC6972719; pdf:https://europepmc.org/articles/PMC6972719?pdf=render" }, + { + "id": "35861824", + "doi": "https://doi.org/10.1161/jaha.121.025935", + "title": "Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.", + "authorString": "Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2022", + "date": "2022-07-13", + "isOpenAccess": "Y", + "keywords": "Biomarkers; Childhood Cancer Survivors; Cardio\u2010oncology; Chemokine Ligands; Anthracycline\u2010related Cardiomyopathy; Cancer Therapy\u2013related Cardiac Dysfunction", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction \u226553% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render" + }, { "id": "35908569", "doi": "https://doi.org/10.1016/s0140-6736(22)01109-6", @@ -30463,6 +30497,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.diabet.2022.101418" }, + { + "id": "32784218", + "doi": "https://doi.org/10.3399/bjgp20x712313", + "title": "Suboptimal prescribing behaviour associated with clinical software design features: a retrospective cohort study in English NHS primary care.", + "authorString": "MacKenna B, Curtis HJ, Walker AJ, Bacon S, Croker R, Goldacre B.", + "authorAffiliations": "", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2020", + "date": "2020-08-27", + "isOpenAccess": "N", + "keywords": "Cohort studies; Primary Care; Clinical Software; Ghost-branded Generics; Drugs Prescribing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Electronic health record (EHR) systems are used by clinicians to record patients' medical information, and support clinical activities such as prescribing. In England, healthcare professionals are advised to 'prescribe generically' because generic drugs are usually cheaper than branded alternatives, and have fixed reimbursement costs. 'Ghost-branded generics' are a new category of medicines savings, caused by prescribers specifying a manufacturer for a generic product, often resulting in a higher reimbursement price compared with the true generic.

Aim

To describe time trends and practice factors associated with excess medication costs from ghost-branded generic prescribing.

Design and setting

Retrospective cohort study of English GP prescribing data and EHR deployment data.

Method

A retrospective cohort study was conducted, based on data from the OpenPrescribing.net database from May 2013 to May 2019. Total spending on ghost-branded generics across England was calculated, and excess spend on ghost-branded generics calculated as a percentage of all spending on generics for every CCG and general practice in England, for every month in the study period.

Results

There were 31.8 million ghost-branded generic items and \u00a39.5 million excess cost in 2018, compared with 7.45 million ghost-branded generic items and \u00a31.3 million excess cost in 2014. Most excess costs were associated with one EHR, SystmOne, and it was identified that SystmOne offered ghost-branded generic options as the default. After informing the vendor, the authors monitored for subsequent change in costs, and report a rapid decrease in ghost-branded generic expenditure.

Conclusion

A design choice in a commonly used EHR has led to \u00a39.5 million in avoidable excess prescribing costs for the NHS in 1 year. Notifying the vendor led to a change in user interface and a rapid, substantial spend reduction. This finding illustrates that EHR user interface design has a substantial impact on the quality, safety, and cost-effectiveness of clinical practice; this should be a priority for quantitative research.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3399/bjgp20X712313; html:https://europepmc.org/articles/PMC7425205; pdf:https://europepmc.org/articles/PMC7425205?pdf=render; doi:https://doi.org/10.3399/bjgp20x712313" + }, { "id": "33012285", "doi": "https://doi.org/10.1186/s12916-020-01779-4", @@ -30481,21 +30532,21 @@ "urls": "doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render" }, { - "id": "32784218", - "doi": "https://doi.org/10.3399/bjgp20x712313", - "title": "Suboptimal prescribing behaviour associated with clinical software design features: a retrospective cohort study in English NHS primary care.", - "authorString": "MacKenna B, Curtis HJ, Walker AJ, Bacon S, Croker R, Goldacre B.", + "id": "32656368", + "doi": "https://doi.org/10.12688/wellcomeopenres.15889.2", + "title": "What settings have been linked to SARS-CoV-2 transmission clusters?", + "authorString": "Leclerc QJ, Fuller NM, Knight LE, CMMID COVID-19 Working Group, Funk S, Knight GM.", "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "journalTitle": "Wellcome open research", "pubYear": "2020", - "date": "2020-08-27", - "isOpenAccess": "N", - "keywords": "Cohort studies; Primary Care; Clinical Software; Ghost-branded Generics; Drugs Prescribing", + "date": "2020-06-05", + "isOpenAccess": "Y", + "keywords": "Transmission; Cluster; Coronavirus; Settings; Lockdown; Covid-19; Sars-cov-2", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Electronic health record (EHR) systems are used by clinicians to record patients' medical information, and support clinical activities such as prescribing. In England, healthcare professionals are advised to 'prescribe generically' because generic drugs are usually cheaper than branded alternatives, and have fixed reimbursement costs. 'Ghost-branded generics' are a new category of medicines savings, caused by prescribers specifying a manufacturer for a generic product, often resulting in a higher reimbursement price compared with the true generic.

Aim

To describe time trends and practice factors associated with excess medication costs from ghost-branded generic prescribing.

Design and setting

Retrospective cohort study of English GP prescribing data and EHR deployment data.

Method

A retrospective cohort study was conducted, based on data from the OpenPrescribing.net database from May 2013 to May 2019. Total spending on ghost-branded generics across England was calculated, and excess spend on ghost-branded generics calculated as a percentage of all spending on generics for every CCG and general practice in England, for every month in the study period.

Results

There were 31.8 million ghost-branded generic items and \u00a39.5 million excess cost in 2018, compared with 7.45 million ghost-branded generic items and \u00a31.3 million excess cost in 2014. Most excess costs were associated with one EHR, SystmOne, and it was identified that SystmOne offered ghost-branded generic options as the default. After informing the vendor, the authors monitored for subsequent change in costs, and report a rapid decrease in ghost-branded generic expenditure.

Conclusion

A design choice in a commonly used EHR has led to \u00a39.5 million in avoidable excess prescribing costs for the NHS in 1 year. Notifying the vendor led to a change in user interface and a rapid, substantial spend reduction. This finding illustrates that EHR user interface design has a substantial impact on the quality, safety, and cost-effectiveness of clinical practice; this should be a priority for quantitative research.", + "abstract": "Background: Concern about the health impact of novel coronavirus SARS-CoV-2 has resulted in widespread enforced reductions in people's movement (\"lockdowns\"). However, there are increasing concerns about the severe economic and wider societal consequences of these measures. Some countries have begun to lift some of the rules on physical distancing in a stepwise manner, with differences in what these \"exit strategies\" entail and their timeframes. The aim of this work was to inform such exit strategies by exploring the types of indoor and outdoor settings where transmission of SARS-CoV-2 has been reported to occur and result in clusters of cases. Identifying potential settings that result in transmission clusters allows these to be kept under close surveillance and/or to remain closed as part of strategies that aim to avoid a resurgence in transmission following the lifting of lockdown measures. Methods: We performed a systematic review of available literature and media reports to find settings reported in peer reviewed articles and media with these characteristics. These sources are curated and made available in an editable online database. Results: We found many examples of SARS-CoV-2 clusters linked to a wide range of mostly indoor settings. Few reports came from schools, many from households, and an increasing number were reported in hospitals and elderly care settings across Europe. Conclusions: We identified possible places that are linked to clusters of COVID-19 cases and could be closely monitored and/or remain closed in the first instance following the progressive removal of lockdown restrictions. However, in part due to the limits in surveillance capacities in many settings, the gathering of information such as cluster sizes and attack rates is limited in several ways: inherent recall bias, biased media reporting and missing data.", "laySummary": "", - "urls": "doi:https://doi.org/10.3399/bjgp20X712313; html:https://europepmc.org/articles/PMC7425205; pdf:https://europepmc.org/articles/PMC7425205?pdf=render; doi:https://doi.org/10.3399/bjgp20x712313" + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15889.2; html:https://europepmc.org/articles/PMC7327724; pdf:https://europepmc.org/articles/PMC7327724?pdf=render" }, { "id": "34645462", @@ -30531,23 +30582,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41591-022-01951-8; pdf:https://www.nature.com/articles/s41591-022-01951-8.pdf" }, - { - "id": "32656368", - "doi": "https://doi.org/10.12688/wellcomeopenres.15889.2", - "title": "What settings have been linked to SARS-CoV-2 transmission clusters?", - "authorString": "Leclerc QJ, Fuller NM, Knight LE, CMMID COVID-19 Working Group, Funk S, Knight GM.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2020", - "date": "2020-06-05", - "isOpenAccess": "Y", - "keywords": "Transmission; Cluster; Coronavirus; Settings; Lockdown; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: Concern about the health impact of novel coronavirus SARS-CoV-2 has resulted in widespread enforced reductions in people's movement (\"lockdowns\"). However, there are increasing concerns about the severe economic and wider societal consequences of these measures. Some countries have begun to lift some of the rules on physical distancing in a stepwise manner, with differences in what these \"exit strategies\" entail and their timeframes. The aim of this work was to inform such exit strategies by exploring the types of indoor and outdoor settings where transmission of SARS-CoV-2 has been reported to occur and result in clusters of cases. Identifying potential settings that result in transmission clusters allows these to be kept under close surveillance and/or to remain closed as part of strategies that aim to avoid a resurgence in transmission following the lifting of lockdown measures. Methods: We performed a systematic review of available literature and media reports to find settings reported in peer reviewed articles and media with these characteristics. These sources are curated and made available in an editable online database. Results: We found many examples of SARS-CoV-2 clusters linked to a wide range of mostly indoor settings. Few reports came from schools, many from households, and an increasing number were reported in hospitals and elderly care settings across Europe. Conclusions: We identified possible places that are linked to clusters of COVID-19 cases and could be closely monitored and/or remain closed in the first instance following the progressive removal of lockdown restrictions. However, in part due to the limits in surveillance capacities in many settings, the gathering of information such as cluster sizes and attack rates is limited in several ways: inherent recall bias, biased media reporting and missing data.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15889.2; html:https://europepmc.org/articles/PMC7327724; pdf:https://europepmc.org/articles/PMC7327724?pdf=render" - }, { "id": "35017564", "doi": "https://doi.org/10.1038/s41467-021-27950-w", @@ -30565,6 +30599,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render" }, + { + "id": "33617936", + "doi": "https://doi.org/10.1016/j.jhin.2021.02.012", + "title": "Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.", + "authorString": "McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.", + "authorAffiliations": "", + "journalTitle": "The Journal of hospital infection", + "pubYear": "2021", + "date": "2021-02-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render" + }, { "id": "37034358", "doi": "https://doi.org/10.1016/j.eclinm.2023.101932", @@ -30583,21 +30634,21 @@ "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.101932; html:https://europepmc.org/articles/PMC10072853; pdf:https://europepmc.org/articles/PMC10072853?pdf=render" }, { - "id": "33617936", - "doi": "https://doi.org/10.1016/j.jhin.2021.02.012", - "title": "Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.", - "authorString": "McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.", + "id": "31675503", + "doi": "https://doi.org/10.1016/j.cell.2019.10.004", + "title": "Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.", + "authorString": "Gurdasani D, Carstensen T, Fatumo S, Chen G, Franklin CS, Prado-Martinez J, Bouman H, Abascal F, Haber M, Tachmazidou I, Mathieson I, Ekoru K, DeGorter MK, Nsubuga RN, Finan C, Wheeler E, Chen L, Cooper DN, Schiffels S, Chen Y, Ritchie GRS, Pollard MO, Fortune MD, Mentzer AJ, Garrison E, Bergstr\u00f6m A, Hatzikotoulas K, Adeyemo A, Doumatey A, Elding H, Wain LV, Ehret G, Auer PL, Kooperberg CL, Reiner AP, Franceschini N, Maher D, Montgomery SB, Kadie C, Widmer C, Xue Y, Seeley J, Asiki G, Kamali A, Young EH, Pomilla C, Soranzo N, Zeggini E, Pirie F, Morris AP, Heckerman D, Tyler-Smith C, Motala AA, Rotimi C, Kaleebu P, Barroso I, Sandhu MS.", "authorAffiliations": "", - "journalTitle": "The Journal of hospital infection", - "pubYear": "2021", - "date": "2021-02-20", - "isOpenAccess": "Y", + "journalTitle": "Cell", + "pubYear": "2019", + "date": "2019-10-01", + "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "", + "abstract": "Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004" }, { "id": "30928767", @@ -30616,23 +30667,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002" }, - { - "id": "31675503", - "doi": "https://doi.org/10.1016/j.cell.2019.10.004", - "title": "Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.", - "authorString": "Gurdasani D, Carstensen T, Fatumo S, Chen G, Franklin CS, Prado-Martinez J, Bouman H, Abascal F, Haber M, Tachmazidou I, Mathieson I, Ekoru K, DeGorter MK, Nsubuga RN, Finan C, Wheeler E, Chen L, Cooper DN, Schiffels S, Chen Y, Ritchie GRS, Pollard MO, Fortune MD, Mentzer AJ, Garrison E, Bergstr\u00f6m A, Hatzikotoulas K, Adeyemo A, Doumatey A, Elding H, Wain LV, Ehret G, Auer PL, Kooperberg CL, Reiner AP, Franceschini N, Maher D, Montgomery SB, Kadie C, Widmer C, Xue Y, Seeley J, Asiki G, Kamali A, Young EH, Pomilla C, Soranzo N, Zeggini E, Pirie F, Morris AP, Heckerman D, Tyler-Smith C, Motala AA, Rotimi C, Kaleebu P, Barroso I, Sandhu MS.", - "authorAffiliations": "", - "journalTitle": "Cell", - "pubYear": "2019", - "date": "2019-10-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004" - }, { "id": "34172543", "doi": "https://doi.org/10.1136/bmjopen-2020-042893", @@ -30684,23 +30718,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/30083; html:https://europepmc.org/articles/PMC8494068" }, - { - "id": "35231023", - "doi": "https://doi.org/10.1371/journal.pmed.1003907", - "title": "Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.", - "authorString": "Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2022", - "date": "2022-03-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render" - }, { "id": "33004356", "doi": "https://doi.org/10.3399/bjgp20x712673", @@ -30718,6 +30735,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3399/bjgp20X712673; html:https://europepmc.org/articles/PMC7518898; pdf:https://europepmc.org/articles/PMC7518898?pdf=render; doi:https://doi.org/10.3399/bjgp20x712673" }, + { + "id": "35231023", + "doi": "https://doi.org/10.1371/journal.pmed.1003907", + "title": "Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.", + "authorString": "Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2022", + "date": "2022-03-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render" + }, { "id": "34600625", "doi": "https://doi.org/10.1016/s0140-6736(21)01609-3", @@ -30939,23 +30973,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.23889/ijpds.v3i1.412; html:https://europepmc.org/articles/PMC7299475; pdf:https://europepmc.org/articles/PMC7299475?pdf=render" }, - { - "id": "33628949", - "doi": "https://doi.org/10.12688/wellcomeopenres.16020.1", - "title": "The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020. ", - "authorString": "Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2020", - "date": "2020-06-10", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across the parent and offspring generations between the 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 partners of offspring). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.\u00a0 Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases fell between 1.03% - 4.19% depending on timing of measurement during the period of reporting. Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16020.1; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render" - }, { "id": "31787481", "doi": "https://doi.org/10.1016/j.schres.2019.10.061", @@ -31041,6 +31058,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijcard.2020.04.068" }, + { + "id": "33628949", + "doi": "https://doi.org/10.12688/wellcomeopenres.16020.1", + "title": "The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020. ", + "authorString": "Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2020", + "date": "2020-06-10", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across the parent and offspring generations between the 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 partners of offspring). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.\u00a0 Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases fell between 1.03% - 4.19% depending on timing of measurement during the period of reporting. Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16020.1; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render" + }, { "id": "31196905", "doi": "https://doi.org/10.1136/bmjopen-2019-028929", @@ -31058,23 +31092,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2019-028929; html:https://europepmc.org/articles/PMC6577359; pdf:https://europepmc.org/articles/PMC6577359?pdf=render" }, - { - "id": "37067557", - "doi": "https://doi.org/10.1007/s00134-023-07039-2", - "title": "Variants of concern and clinical outcomes in critically ill COVID-19 patients.", - "authorString": "DP-EFFECT-BRAZIL investigators.", - "authorAffiliations": "", - "journalTitle": "Intensive care medicine", - "pubYear": "2023", - "date": "2023-04-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render" - }, { "id": "33430602", "doi": "https://doi.org/10.1161/circheartfailure.120.007022", @@ -31092,6 +31109,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render" }, + { + "id": "37067557", + "doi": "https://doi.org/10.1007/s00134-023-07039-2", + "title": "Variants of concern and clinical outcomes in critically ill COVID-19 patients.", + "authorString": "DP-EFFECT-BRAZIL investigators.", + "authorAffiliations": "", + "journalTitle": "Intensive care medicine", + "pubYear": "2023", + "date": "2023-04-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render" + }, { "id": "32814899", "doi": "https://doi.org/10.1038/s41586-020-2635-8", @@ -31126,23 +31160,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-056541; html:https://europepmc.org/articles/PMC9058769; pdf:https://europepmc.org/articles/PMC9058769?pdf=render" }, - { - "id": "37263751", - "doi": "https://doi.org/10.1183/13993003.01667-2022", - "title": "Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.", - "authorString": "Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.", - "authorAffiliations": "", - "journalTitle": "The European respiratory journal", - "pubYear": "2023", - "date": "2023-06-15", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5\u00d710-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48\u2009471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17\u2009627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render" - }, { "id": "33777379", "doi": "https://doi.org/10.1093/ckj/sfaa045", @@ -31160,6 +31177,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ckj/sfaa045; html:https://europepmc.org/articles/PMC7986362; pdf:https://europepmc.org/articles/PMC7986362?pdf=render" }, + { + "id": "37263751", + "doi": "https://doi.org/10.1183/13993003.01667-2022", + "title": "Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.", + "authorString": "Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.", + "authorAffiliations": "", + "journalTitle": "The European respiratory journal", + "pubYear": "2023", + "date": "2023-06-15", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5\u00d710-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48\u2009471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17\u2009627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render" + }, { "id": "34568827", "doi": "https://doi.org/10.1093/schizbullopen/sgab041", @@ -31398,23 +31432,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-020-14717-y; html:https://europepmc.org/articles/PMC7033171; pdf:https://europepmc.org/articles/PMC7033171?pdf=render" }, - { - "id": "36436752", - "doi": "https://doi.org/10.1016/j.ijid.2022.11.024", - "title": "Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.", - "authorString": "Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.", - "authorAffiliations": "", - "journalTitle": "International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases", - "pubYear": "2023", - "date": "2022-11-24", - "isOpenAccess": "Y", - "keywords": "Covid-19; Omicron; Ba.4; Death, Severe Hospitalization; Ba.5", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

Methods

We included public sector patients aged \u226520 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.

Results

Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.

Conclusion

Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render; doi:https://doi.org/10.1016/j.ijid.2022.11.024" - }, { "id": "32289242", "doi": "https://doi.org/10.1098/rsob.190297", @@ -31432,6 +31449,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1098/rsob.190297; html:https://europepmc.org/articles/PMC7241076; pdf:https://europepmc.org/articles/PMC7241076?pdf=render" }, + { + "id": "36436752", + "doi": "https://doi.org/10.1016/j.ijid.2022.11.024", + "title": "Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.", + "authorString": "Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.", + "authorAffiliations": "", + "journalTitle": "International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases", + "pubYear": "2023", + "date": "2022-11-24", + "isOpenAccess": "Y", + "keywords": "Covid-19; Omicron; Ba.4; Death, Severe Hospitalization; Ba.5", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

Methods

We included public sector patients aged \u226520 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.

Results

Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.

Conclusion

Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render; doi:https://doi.org/10.1016/j.ijid.2022.11.024" + }, { "id": "36029521", "doi": "https://doi.org/10.1093/ije/dyac171", @@ -31823,23 +31857,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12916-020-01790-9; html:https://europepmc.org/articles/PMC7577796; pdf:https://europepmc.org/articles/PMC7577796?pdf=render" }, - { - "id": "35296488", - "doi": "https://doi.org/10.1136/bmjopen-2021-058552", - "title": "AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353\u2009157 patients in London, UK.", - "authorString": "Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-03-16", - "isOpenAccess": "Y", - "keywords": "Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353\u2009157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353\u2009157 individuals, 186\u2009651 had a total of 1\u2009337\u2009711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12\u2009022 patients with myocardial infarction, 11\u2009735 with all-cause stroke and 13\u2009363 with all-cause dementia. A total of 6\u2009261\u2009931 retinal images of seven different modalities and across three manufacturers were acquired from 1\u200954\u2009830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render" - }, { "id": "31862893", "doi": "https://doi.org/10.1038/s41467-019-13848-1", @@ -31857,6 +31874,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-019-13848-1; html:https://europepmc.org/articles/PMC6925280; pdf:https://europepmc.org/articles/PMC6925280?pdf=render" }, + { + "id": "35296488", + "doi": "https://doi.org/10.1136/bmjopen-2021-058552", + "title": "AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353\u2009157 patients in London, UK.", + "authorString": "Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-03-16", + "isOpenAccess": "Y", + "keywords": "Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353\u2009157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353\u2009157 individuals, 186\u2009651 had a total of 1\u2009337\u2009711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12\u2009022 patients with myocardial infarction, 11\u2009735 with all-cause stroke and 13\u2009363 with all-cause dementia. A total of 6\u2009261\u2009931 retinal images of seven different modalities and across three manufacturers were acquired from 1\u200954\u2009830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render" + }, { "id": "33623826", "doi": "https://doi.org/10.12688/wellcomeopenres.16164.2", @@ -31872,7 +31906,7 @@ "healthCategories": "", "abstract": "Background: \u200b During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: \u200b We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. Results:\u00a0 Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. Conclusions: \u200b If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.", "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render" + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render; doi:https://doi.org/10.12688/wellcomeopenres.16164.2" }, { "id": "36269859", @@ -31942,23 +31976,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?pdf=render" }, - { - "id": "37393924", - "doi": "https://doi.org/10.1016/s0140-6736(23)00860-7", - "title": "The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.", - "authorString": "GBD 2019 Child and Adolescent Communicable Disease Collaborators.", - "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2023", - "date": "2023-06-29", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3\u00b70 million deaths and 30\u00b70 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288\u00b74 million DALYs from communicable diseases among children and adolescents globally (57\u00b73% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4\u00b70 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59\u00b78% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render" - }, { "id": "32546850", "doi": "https://doi.org/10.1038/s41598-020-66737-9", @@ -31976,6 +31993,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render" }, + { + "id": "37393924", + "doi": "https://doi.org/10.1016/s0140-6736(23)00860-7", + "title": "The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.", + "authorString": "GBD 2019 Child and Adolescent Communicable Disease Collaborators.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2023", + "date": "2023-06-29", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3\u00b70 million deaths and 30\u00b70 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288\u00b74 million DALYs from communicable diseases among children and adolescents globally (57\u00b73% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4\u00b70 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59\u00b78% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render" + }, { "id": "34321180", "doi": "https://doi.org/10.1016/j.aucc.2021.05.013", @@ -32384,6 +32418,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41598-020-76518-z; html:https://europepmc.org/articles/PMC7672070; pdf:https://europepmc.org/articles/PMC7672070?pdf=render" }, + { + "id": "31794059", + "doi": "https://doi.org/10.1111/bjd.18778", + "title": "What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.", + "authorString": "Blakeway H, Van-de-Velde V, Allen VB, Kravvas G, Palla L, Page MJ, Flohr C, Weller RB, Irvine AD, McPherson T, Roberts A, Williams HC, Reynolds N, Brown SJ, Paternoster L, Langan SM, (on behalf of UK TREND Eczema Network).", + "authorAffiliations": "", + "journalTitle": "The British journal of dermatology", + "pubYear": "2020", + "date": "2020-02-11", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD).

Objectives

To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations.

Methods

A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis.

Results

Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction \u2264 0\u00b705), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions.

Conclusions

Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment:\u00a0Park and Seo. Br J Dermatol 2020; 183:411.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/bjd.18778; html:https://europepmc.org/articles/PMC7496176; pdf:https://europepmc.org/articles/PMC7496176?pdf=render" + }, { "id": "30772400", "doi": "https://doi.org/10.1016/j.neuroimage.2019.02.028", @@ -32402,21 +32453,21 @@ "urls": "doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; html:https://europepmc.org/articles/PMC6503942" }, { - "id": "31794059", - "doi": "https://doi.org/10.1111/bjd.18778", - "title": "What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.", - "authorString": "Blakeway H, Van-de-Velde V, Allen VB, Kravvas G, Palla L, Page MJ, Flohr C, Weller RB, Irvine AD, McPherson T, Roberts A, Williams HC, Reynolds N, Brown SJ, Paternoster L, Langan SM, (on behalf of UK TREND Eczema Network).", + "id": "33972514", + "doi": "https://doi.org/10.1038/s41467-021-22338-2", + "title": "Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.", + "authorString": "Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, J\u00e4rvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.", "authorAffiliations": "", - "journalTitle": "The British journal of dermatology", - "pubYear": "2020", - "date": "2020-02-11", + "journalTitle": "Nature communications", + "pubYear": "2021", + "date": "2021-05-10", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD).

Objectives

To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations.

Methods

A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis.

Results

Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction \u2264 0\u00b705), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions.

Conclusions

Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment:\u00a0Park and Seo. Br J Dermatol 2020; 183:411.", + "abstract": "Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.", "laySummary": "", - "urls": "doi:https://doi.org/10.1111/bjd.18778; html:https://europepmc.org/articles/PMC7496176; pdf:https://europepmc.org/articles/PMC7496176?pdf=render" + "urls": "doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render; pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf" }, { "id": "32336304", @@ -32435,23 +32486,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1192/j.eurpsy.2020.39; html:https://europepmc.org/articles/PMC7355164; pdf:https://europepmc.org/articles/PMC7355164?pdf=render" }, - { - "id": "33972514", - "doi": "https://doi.org/10.1038/s41467-021-22338-2", - "title": "Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.", - "authorString": "Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, J\u00e4rvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2021", - "date": "2021-05-10", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render; pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf" - }, { "id": "32681152", "doi": "https://doi.org/10.1038/s41596-020-0343-3", @@ -33234,23 +33268,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/mds.29147; html:https://europepmc.org/articles/PMC9796674; pdf:https://europepmc.org/articles/PMC9796674?pdf=render" }, - { - "id": "35143473", - "doi": "https://doi.org/10.1371/journal.pbio.3001531", - "title": "SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.", - "authorString": "Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.", - "authorAffiliations": "", - "journalTitle": "PLoS biology", - "pubYear": "2022", - "date": "2022-02-10", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render" - }, { "id": "31711539", "doi": "https://doi.org/10.1186/s13326-019-0211-7", @@ -33269,38 +33286,38 @@ "urls": "doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render" }, { - "id": "35337642", - "doi": "https://doi.org/10.1016/s2589-7500(22)00018-8", - "title": "Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.", - "authorString": "N\u00e4rhi F, Moonesinghe SR, Shenkin SD, Drake TM, Mulholland RH, Donegan C, Dunning J, Fairfield CJ, Girvan M, Hardwick HE, Ho A, Leeming G, Nguyen-Van-Tam JS, Pius R, Russell CD, Shaw CA, Spencer RG, Turtle L, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, Docherty AB, ISARIC4C investigators.", + "id": "35143473", + "doi": "https://doi.org/10.1371/journal.pbio.3001531", + "title": "SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.", + "authorString": "Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.", "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", + "journalTitle": "PLoS biology", "pubYear": "2022", - "date": "2022-04-01", + "date": "2022-02-10", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods

We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.

Findings

Between June 17, 2020, and April 14, 2021, 47\u2008795 (75\u00b72%) of 63\u2008525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11\u2008185 [86\u00b76%] of 12\u2008909 vs 36\u2008415 [72\u00b74%] of 50\u2008278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0\u00b779 [95% CI 0\u00b770-0\u00b789], p=0\u00b70001, for 70-79 years; 0\u00b752 [0\u00b746-0\u00b758], p<0\u00b70001, for >80 years), independent of patient demographics and illness severity. 84 (54\u00b72%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27\u00b75% in the week before June 16, 2020, to 75-80% in January, 2021.

Interpretation

Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.

Funding

UK National Institute for Health Research and UK Medical Research Council.", + "abstract": "Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00018-8; html:https://europepmc.org/articles/PMC8940185; pdf:http://www.thelancet.com/article/S2589750022000188/pdf" + "urls": "doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render" }, { - "id": "35112706", - "doi": "https://doi.org/10.1242/dmm.049257", - "title": "Molecular Subtyping Resource: a user-friendly tool for rapid biological discovery from transcriptional data.", - "authorString": "Ahmaderaghi B, Amirkhah R, Jackson J, Lannagan TRM, Gilroy K, Malla SB, Redmond KL, Quinn G, McDade SS, ACRCelerate Consortium, Maughan T, Leedham S, Campbell ASD, Sansom OJ, Lawler M, Dunne PD.", + "id": "35337642", + "doi": "https://doi.org/10.1016/s2589-7500(22)00018-8", + "title": "Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.", + "authorString": "N\u00e4rhi F, Moonesinghe SR, Shenkin SD, Drake TM, Mulholland RH, Donegan C, Dunning J, Fairfield CJ, Girvan M, Hardwick HE, Ho A, Leeming G, Nguyen-Van-Tam JS, Pius R, Russell CD, Shaw CA, Spencer RG, Turtle L, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, Docherty AB, ISARIC4C investigators.", "authorAffiliations": "", - "journalTitle": "Disease models & mechanisms", + "journalTitle": "The Lancet. Digital health", "pubYear": "2022", - "date": "2022-03-30", + "date": "2022-04-01", "isOpenAccess": "Y", - "keywords": "Bioinformatics; Rna-seq; Data Analytics", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Generation of transcriptional data has dramatically increased in the past decade, driving the development of analytical algorithms that enable interrogation of the biology underpinning the profiled samples. However, these resources require users to have expertise in data wrangling and analytics, reducing opportunities for biological discovery by 'wet-lab' users with a limited programming skillset. Although commercial solutions exist, costs for software access can be prohibitive for academic research groups. To address these challenges, we have developed an open source and user-friendly data analysis platform for on-the-fly bioinformatic interrogation of transcriptional data derived from human or mouse tissue, called Molecular Subtyping Resource (MouSR). This internet-accessible analytical tool, https://mousr.qub.ac.uk/, enables users to easily interrogate their data using an intuitive 'point-and-click' interface, which includes a suite of molecular characterisation options including quality control, differential gene expression, gene set enrichment and microenvironmental cell population analyses from RNA sequencing. The MouSR online tool provides a unique freely available option for users to perform rapid transcriptomic analyses and comprehensive interrogation of the signalling underpinning transcriptional datasets, which alleviates a major bottleneck for biological discovery. This article has an associated First Person interview with the first author of the paper.", + "abstract": "

Background

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods

We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.

Findings

Between June 17, 2020, and April 14, 2021, 47\u2008795 (75\u00b72%) of 63\u2008525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11\u2008185 [86\u00b76%] of 12\u2008909 vs 36\u2008415 [72\u00b74%] of 50\u2008278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0\u00b779 [95% CI 0\u00b770-0\u00b789], p=0\u00b70001, for 70-79 years; 0\u00b752 [0\u00b746-0\u00b758], p<0\u00b70001, for >80 years), independent of patient demographics and illness severity. 84 (54\u00b72%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27\u00b75% in the week before June 16, 2020, to 75-80% in January, 2021.

Interpretation

Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.

Funding

UK National Institute for Health Research and UK Medical Research Council.", "laySummary": "", - "urls": "doi:https://doi.org/10.1242/dmm.049257; html:https://europepmc.org/articles/PMC8990914; doi:https://doi.org/10.1242/dmm.049257" + "urls": "doi:https://doi.org/10.1016/S2589-7500(22)00018-8; html:https://europepmc.org/articles/PMC8940185; pdf:http://www.thelancet.com/article/S2589750022000188/pdf" }, { "id": "34151270", @@ -33319,6 +33336,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render" }, + { + "id": "35112706", + "doi": "https://doi.org/10.1242/dmm.049257", + "title": "Molecular Subtyping Resource: a user-friendly tool for rapid biological discovery from transcriptional data.", + "authorString": "Ahmaderaghi B, Amirkhah R, Jackson J, Lannagan TRM, Gilroy K, Malla SB, Redmond KL, Quinn G, McDade SS, ACRCelerate Consortium, Maughan T, Leedham S, Campbell ASD, Sansom OJ, Lawler M, Dunne PD.", + "authorAffiliations": "", + "journalTitle": "Disease models & mechanisms", + "pubYear": "2022", + "date": "2022-03-30", + "isOpenAccess": "Y", + "keywords": "Bioinformatics; Rna-seq; Data Analytics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Generation of transcriptional data has dramatically increased in the past decade, driving the development of analytical algorithms that enable interrogation of the biology underpinning the profiled samples. However, these resources require users to have expertise in data wrangling and analytics, reducing opportunities for biological discovery by 'wet-lab' users with a limited programming skillset. Although commercial solutions exist, costs for software access can be prohibitive for academic research groups. To address these challenges, we have developed an open source and user-friendly data analysis platform for on-the-fly bioinformatic interrogation of transcriptional data derived from human or mouse tissue, called Molecular Subtyping Resource (MouSR). This internet-accessible analytical tool, https://mousr.qub.ac.uk/, enables users to easily interrogate their data using an intuitive 'point-and-click' interface, which includes a suite of molecular characterisation options including quality control, differential gene expression, gene set enrichment and microenvironmental cell population analyses from RNA sequencing. The MouSR online tool provides a unique freely available option for users to perform rapid transcriptomic analyses and comprehensive interrogation of the signalling underpinning transcriptional datasets, which alleviates a major bottleneck for biological discovery. This article has an associated First Person interview with the first author of the paper.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1242/dmm.049257; html:https://europepmc.org/articles/PMC8990914; doi:https://doi.org/10.1242/dmm.049257" + }, { "id": "33174830", "doi": "https://doi.org/10.1099/mgen.0.000453", @@ -33353,23 +33387,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2021-052629; html:https://europepmc.org/articles/PMC8395280; pdf:https://europepmc.org/articles/PMC8395280?pdf=render" }, - { - "id": "36845321", - "doi": "https://doi.org/10.12688/wellcomeopenres.17403.2", - "title": "Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.", - "authorString": "Moreno-Martos D, Verhamme K, Ostropolets A, Kostka K, Duarte-Sales T, Prieto-Alhambra D, Alshammari TM, Alghoul H, Ahmed WU, Blacketer C, DuVall S, Lai L, Matheny M, Nyberg F, Posada J, Rijnbeek P, Spotnitz M, Sena A, Shah N, Suchard M, Chan You S, Hripcsak G, Ryan P, Morales D.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2022", - "date": "2022-03-24", - "isOpenAccess": "Y", - "keywords": "COPD; Coronavirus; Epidemiology.; Sars-cov-2; Covid", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. \u00a0 Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render" - }, { "id": "32423943", "doi": "https://doi.org/10.1136/bmjopen-2020-038974", @@ -33387,6 +33404,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render" }, + { + "id": "36845321", + "doi": "https://doi.org/10.12688/wellcomeopenres.17403.2", + "title": "Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.", + "authorString": "Moreno-Martos D, Verhamme K, Ostropolets A, Kostka K, Duarte-Sales T, Prieto-Alhambra D, Alshammari TM, Alghoul H, Ahmed WU, Blacketer C, DuVall S, Lai L, Matheny M, Nyberg F, Posada J, Rijnbeek P, Spotnitz M, Sena A, Shah N, Suchard M, Chan You S, Hripcsak G, Ryan P, Morales D.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2022", + "date": "2022-03-24", + "isOpenAccess": "Y", + "keywords": "COPD; Coronavirus; Epidemiology.; Sars-cov-2; Covid", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. \u00a0 Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render" + }, { "id": "31331193", "doi": "https://doi.org/10.1161/circulationaha.119.041546", @@ -33589,7 +33623,7 @@ "healthCategories": "", "abstract": "A serious obstacle to the development of Natural Language Processing (NLP) methods in the clinical domain is the accessibility of textual data. The mental health domain is particularly challenging, partly because clinical documentation relies heavily on free text that is difficult to de-identify completely. This problem could be tackled by using artificial medical data. In this work, we present an approach to generate artificial clinical documents. We apply this approach to discharge summaries from a large mental healthcare provider and discharge summaries from an intensive care unit. We perform an extensive intrinsic evaluation where we (1) apply several measures of text preservation; (2) measure how much the model memorises training data; and (3) estimate clinical validity of the generated text based on a human evaluation task. Furthermore, we perform an extrinsic evaluation by studying the impact of using artificial text in a downstream NLP text classification task. We found that using this artificial data as training data can lead to classification results that are comparable to the original results. Additionally, using only a small amount of information from the original data to condition the generation of the artificial data is successful, which holds promise for reducing the risk of these artificial data retaining rare information from the original data. This is an important finding for our long-term goal of being able to generate artificial clinical data that can be released to the wider research community and accelerate advances in developing computational methods that use healthcare data.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render" + "urls": "doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render; pdf:https://www.nature.com/articles/s41746-020-0267-x.pdf" }, { "id": "31197928", @@ -33965,23 +33999,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render" }, - { - "id": "35484151", - "doi": "https://doi.org/10.1038/s41467-022-29932-y", - "title": "Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.", - "authorString": "Richardson TG, Crouch DJM, Power GM, Morales-Berstein F, Hazelwood E, Fang S, Cho Y, Inshaw JRJ, Robertson CC, Sidore C, Cucca F, Rich SS, Todd JA, Davey Smith G.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2022", - "date": "2022-04-28", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR\u2009=\u20092.05 per change in body size category, 95% CI\u2009=\u20091.20 to 3.50, P\u2009=\u20090.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR\u2009=\u20092.32, 95% CI\u2009=\u20091.21 to 4.42, P\u2009=\u20090.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n\u2009=\u200915,573 cases and n\u2009=\u2009158,408 controls (OR\u2009=\u20091.94, 95% CI\u2009=\u20091.21 to 3.12, P\u2009=\u20090.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-022-29932-y; html:https://europepmc.org/articles/PMC9051135; pdf:https://europepmc.org/articles/PMC9051135?pdf=render" - }, { "id": "33323250", "doi": "https://doi.org/10.1016/s2589-7500(19)30121-9", @@ -33999,6 +34016,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S2589-7500(19)30121-9" }, + { + "id": "35484151", + "doi": "https://doi.org/10.1038/s41467-022-29932-y", + "title": "Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.", + "authorString": "Richardson TG, Crouch DJM, Power GM, Morales-Berstein F, Hazelwood E, Fang S, Cho Y, Inshaw JRJ, Robertson CC, Sidore C, Cucca F, Rich SS, Todd JA, Davey Smith G.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2022", + "date": "2022-04-28", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR\u2009=\u20092.05 per change in body size category, 95% CI\u2009=\u20091.20 to 3.50, P\u2009=\u20090.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR\u2009=\u20092.32, 95% CI\u2009=\u20091.21 to 4.42, P\u2009=\u20090.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n\u2009=\u200915,573 cases and n\u2009=\u2009158,408 controls (OR\u2009=\u20091.94, 95% CI\u2009=\u20091.21 to 3.12, P\u2009=\u20090.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41467-022-29932-y; html:https://europepmc.org/articles/PMC9051135; pdf:https://europepmc.org/articles/PMC9051135?pdf=render" + }, { "id": "32597303", "doi": "https://doi.org/10.1080/15476286.2020.1777768", @@ -34050,23 +34084,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pgen.1009436; html:https://europepmc.org/articles/PMC8553134; pdf:https://europepmc.org/articles/PMC8553134?pdf=render; pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009436&type=printable" }, - { - "id": "36258219", - "doi": "https://doi.org/10.1186/s13063-022-06824-6", - "title": "Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.", - "authorString": "Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.", - "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2022", - "date": "2022-10-18", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aim

To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.

Methods and findings

During the first 24\u00a0months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving\u2009>\u200945,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab\u2009+\u2009imdevimab, and tocilizumab.

Conclusions

RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render" - }, { "id": "31408153", "doi": "https://doi.org/10.1093/europace/euz220", @@ -34084,6 +34101,23 @@ "laySummary": "This study identified EHR records of AF and vavular heard disease in over 70k UK individuals and looked for associations with stroke, systemic embolism and mortality. They used CALIBER - a data source connecting office of national statistics, CPRD and HES data from over 10 years. They reported clear methodology on how the EHR was used to classify disease, showed overall prevalence change in different AF related diseases over time, and were able to provide insights at a more granular level - for example, valvular heart disease subtypes in AF than previous studies. The full code list (EHR codes) is provided in supplement, so methods are theoretically reproducible. Immediate impact to patient is less strong and there is wasn't much emphasis on diversity and inclusion.", "urls": "doi:https://doi.org/10.1093/europace/euz220; html:https://europepmc.org/articles/PMC6888023; pdf:https://europepmc.org/articles/PMC6888023?pdf=render" }, + { + "id": "36258219", + "doi": "https://doi.org/10.1186/s13063-022-06824-6", + "title": "Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.", + "authorString": "Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.", + "authorAffiliations": "", + "journalTitle": "Trials", + "pubYear": "2022", + "date": "2022-10-18", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aim

To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.

Methods and findings

During the first 24\u00a0months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving\u2009>\u200945,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab\u2009+\u2009imdevimab, and tocilizumab.

Conclusions

RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render" + }, { "id": "31978332", "doi": "https://doi.org/10.1016/j.ajhg.2020.01.003", @@ -35665,23 +35699,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41588-020-00764-0; html:https://europepmc.org/articles/PMC8240954; pdf:https://europepmc.org/articles/PMC8240954?pdf=render; doi:https://doi.org/10.1038/s41588-020-00764-0; pdf:https://openaccess.sgul.ac.uk/id/eprint/113790/1/EMS128763.pdf" }, - { - "id": "36982069", - "doi": "https://doi.org/10.3390/ijerph20065161", - "title": "The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.", - "authorString": "Lavalle R, Condominas E, Haro JM, Gin\u00e9-V\u00e1zquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Pe\u00f1arrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.", - "authorAffiliations": "", - "journalTitle": "International journal of environmental research and public health", - "pubYear": "2023", - "date": "2023-03-15", - "isOpenAccess": "Y", - "keywords": "Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the \"new normality\", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render" - }, { "id": "29899974", "doi": "https://doi.org/10.12688/f1000research.13830.2", @@ -35699,6 +35716,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/f1000research.13830.2; html:https://europepmc.org/articles/PMC5968362; pdf:https://europepmc.org/articles/PMC5968362?pdf=render" }, + { + "id": "36982069", + "doi": "https://doi.org/10.3390/ijerph20065161", + "title": "The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.", + "authorString": "Lavalle R, Condominas E, Haro JM, Gin\u00e9-V\u00e1zquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Pe\u00f1arrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.", + "authorAffiliations": "", + "journalTitle": "International journal of environmental research and public health", + "pubYear": "2023", + "date": "2023-03-15", + "isOpenAccess": "Y", + "keywords": "Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the \"new normality\", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render" + }, { "id": "33421867", "doi": "https://doi.org/10.1016/j.jad.2020.12.053", @@ -35733,23 +35767,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s13063-021-05284-8; html:https://europepmc.org/articles/PMC8178870; pdf:https://europepmc.org/articles/PMC8178870?pdf=render" }, - { - "id": "33050951", - "doi": "https://doi.org/10.1186/s12916-020-01789-2", - "title": "Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.", - "authorString": "van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2020", - "date": "2020-10-14", - "isOpenAccess": "Y", - "keywords": "Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods

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

Results

We predicted median symptomatic attack rates over the first 12\u2009months of 23% (Niger) to 42% (Mauritius), peaking at 2-4\u2009months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3\u2009months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.

Conclusions

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render" - }, { "id": "33420068", "doi": "https://doi.org/10.1038/s41541-020-00267-3", @@ -35767,6 +35784,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41541-020-00267-3; html:https://europepmc.org/articles/PMC7794334; pdf:https://europepmc.org/articles/PMC7794334?pdf=render" }, + { + "id": "33050951", + "doi": "https://doi.org/10.1186/s12916-020-01789-2", + "title": "Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.", + "authorString": "van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2020", + "date": "2020-10-14", + "isOpenAccess": "Y", + "keywords": "Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

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

Results

We predicted median symptomatic attack rates over the first 12\u2009months of 23% (Niger) to 42% (Mauritius), peaking at 2-4\u2009months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3\u2009months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.

Conclusions

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render" + }, { "id": "34635854", "doi": "https://doi.org/10.1038/s41591-021-01517-0", @@ -35937,23 +35971,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/braincomms/fcab291; html:https://europepmc.org/articles/PMC8853724; pdf:https://europepmc.org/articles/PMC8853724?pdf=render" }, - { - "id": "35304391", - "doi": "https://doi.org/10.1136/bmjopen-2021-050610", - "title": "Results of a pilot feasibility randomised controlled trial exploring the use of an electronic patient-reported outcome measure in the management of UK patients with advanced chronic kidney disease.", - "authorString": "Kyte D, Anderson N, Bishop J, Bissell A, Brettell E, Calvert M, Chadburn M, Cockwell P, Dutton M, Eddington H, Forster E, Hadley G, Ives NJ, Jackson LJ, O'Brien S, Price G, Sharpe K, Stringer S, Verdi R, Waters J, Wilcockson A.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-03-18", - "isOpenAccess": "Y", - "keywords": "Clinical Trials; Nephrology; End Stage Renal Failure", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

The use of routine remote follow-up of patients with chronic kidney disease (CKD) is increasing exponentially. It has been suggested that online electronic patient-reported outcome measures (ePROMs) could be used in parallel, to facilitate real-time symptom monitoring aimed at improving outcomes. We tested the feasibility of this approach in a pilot trial of ePROM symptom monitoring versus usual care in patients with advanced CKD not on dialysis.

Design

A 12-month, parallel, pilot randomised controlled trial (RCT) and qualitative substudy.

Setting and participants

Queen Elizabeth Hospital Birmingham, UK. Adult patients with advanced CKD (estimated glomerular filtration rate \u22656 and \u226415 mL/min/1.73 m2, or a projected risk of progression to kidney failure within 2 years \u226520%).

Intervention

Monthly online ePROM symptom reporting, including automated feedback of tailored self-management advice and triggered clinical notifications in the advent of severe symptoms. Real-time ePROM data were made available to the clinical team via the electronic medical record.

Outcomes

Feasibility (recruitment and retention rates, and acceptability/adherence to the ePROM intervention). Health-related quality of life, clinical data (eg, measures of kidney function, kidney failure, hospitalisation, death) and healthcare utilisation.

Results

52 patients were randomised (31% of approached). Case report form returns were high (99.5%), as was retention (96%). Overall, 73% of expected ePROM questionnaires were received. Intervention adherence was high beyond 90 days (74%) and 180 days (65%); but dropped beyond 270 days (46%). Qualitative interviews supported proof of concept and intervention acceptability, but highlighted necessary changes aimed at enhancing overall functionality/scalability of the ePROM system.

Limitations

Small sample size.

Conclusions

This pilot trial demonstrates that patients are willing to be randomised to a trial assessing ePROM symptom monitoring. The intervention was considered acceptable; though measures to improve longer-term engagement are needed. A full-scale RCT is considered feasible.

Trial registration number

ISRCTN12669006 and the UK NIHR Portfolio (CPMS ID: 36497).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2021-050610; html:https://europepmc.org/articles/PMC8935185; pdf:https://europepmc.org/articles/PMC8935185?pdf=render" - }, { "id": "32543438", "doi": "https://doi.org/10.1016/j.healthplace.2020.102355", @@ -35971,6 +35988,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.healthplace.2020.102355; html:https://europepmc.org/articles/PMC7214342" }, + { + "id": "35304391", + "doi": "https://doi.org/10.1136/bmjopen-2021-050610", + "title": "Results of a pilot feasibility randomised controlled trial exploring the use of an electronic patient-reported outcome measure in the management of UK patients with advanced chronic kidney disease.", + "authorString": "Kyte D, Anderson N, Bishop J, Bissell A, Brettell E, Calvert M, Chadburn M, Cockwell P, Dutton M, Eddington H, Forster E, Hadley G, Ives NJ, Jackson LJ, O'Brien S, Price G, Sharpe K, Stringer S, Verdi R, Waters J, Wilcockson A.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-03-18", + "isOpenAccess": "Y", + "keywords": "Clinical Trials; Nephrology; End Stage Renal Failure", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

The use of routine remote follow-up of patients with chronic kidney disease (CKD) is increasing exponentially. It has been suggested that online electronic patient-reported outcome measures (ePROMs) could be used in parallel, to facilitate real-time symptom monitoring aimed at improving outcomes. We tested the feasibility of this approach in a pilot trial of ePROM symptom monitoring versus usual care in patients with advanced CKD not on dialysis.

Design

A 12-month, parallel, pilot randomised controlled trial (RCT) and qualitative substudy.

Setting and participants

Queen Elizabeth Hospital Birmingham, UK. Adult patients with advanced CKD (estimated glomerular filtration rate \u22656 and \u226415 mL/min/1.73 m2, or a projected risk of progression to kidney failure within 2 years \u226520%).

Intervention

Monthly online ePROM symptom reporting, including automated feedback of tailored self-management advice and triggered clinical notifications in the advent of severe symptoms. Real-time ePROM data were made available to the clinical team via the electronic medical record.

Outcomes

Feasibility (recruitment and retention rates, and acceptability/adherence to the ePROM intervention). Health-related quality of life, clinical data (eg, measures of kidney function, kidney failure, hospitalisation, death) and healthcare utilisation.

Results

52 patients were randomised (31% of approached). Case report form returns were high (99.5%), as was retention (96%). Overall, 73% of expected ePROM questionnaires were received. Intervention adherence was high beyond 90 days (74%) and 180 days (65%); but dropped beyond 270 days (46%). Qualitative interviews supported proof of concept and intervention acceptability, but highlighted necessary changes aimed at enhancing overall functionality/scalability of the ePROM system.

Limitations

Small sample size.

Conclusions

This pilot trial demonstrates that patients are willing to be randomised to a trial assessing ePROM symptom monitoring. The intervention was considered acceptable; though measures to improve longer-term engagement are needed. A full-scale RCT is considered feasible.

Trial registration number

ISRCTN12669006 and the UK NIHR Portfolio (CPMS ID: 36497).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2021-050610; html:https://europepmc.org/articles/PMC8935185; pdf:https://europepmc.org/articles/PMC8935185?pdf=render" + }, { "id": "32376654", "doi": "https://doi.org/10.1136/bmj.m1203", @@ -36822,38 +36856,38 @@ "urls": "doi:https://doi.org/10.1016/j.ebiom.2021.103414; html:https://europepmc.org/articles/PMC8176919; pdf:https://europepmc.org/articles/PMC8176919?pdf=render" }, { - "id": "33536631", - "doi": "https://doi.org/10.1038/s42003-020-01575-z", - "title": "A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.", - "authorString": "Bell S, Rigas AS, Magnusson MK, Ferkingstad E, Allara E, Bjornsdottir G, Ramond A, S\u00f8rensen E, Halldorsson GH, Paul DS, Burgdorf KS, Eggertsson HP, Howson JMM, Th\u00f8rner LW, Kristmundsdottir S, Astle WJ, Erikstrup C, Sigurdsson JK, Vuckovic D, Dinh KM, Tragante V, Surendran P, Pedersen OB, Vidarsson B, Jiang T, Paarup HM, Onundarson PT, Akbari P, Nielsen KR, Lund SH, Juliusson K, Magnusson MI, Frigge ML, Oddsson A, Olafsson I, Kaptoge S, Hjalgrim H, Runarsson G, Wood AM, Jonsdottir I, Hansen TF, Sigurdardottir O, Stefansson H, Rye D, DBDS Genomic Consortium, Peters JE, Westergaard D, Holm H, Soranzo N, Banasik K, Thorleifsson G, Ouwehand WH, Thorsteinsdottir U, Roberts DJ, Sulem P, Butterworth AS, Gudbjartsson DF, Danesh J, Brunak S, Di Angelantonio E, Ullum H, Stefansson K.", + "id": "33737413", + "doi": "https://doi.org/10.1136/bmj.n628", + "title": "Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England.", + "authorString": "Forbes H, Morton CE, Bacon S, McDonald HI, Minassian C, Brown JP, Rentsch CT, Mathur R, Schultze A, DeVito NJ, MacKenna B, Hulme WJ, Croker R, Walker AJ, Williamson EJ, Bates C, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Drysdale H, Wong AYS, Cockburn J, McManus R, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Evans SJW, Bhaskaran K, Eggo RM, Goldacre B, Tomlinson LA.", "authorAffiliations": "", - "journalTitle": "Communications biology", + "journalTitle": "BMJ (Clinical research ed.)", "pubYear": "2021", - "date": "2021-02-03", + "date": "2021-03-18", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N\u2009=\u2009246,139), total iron binding capacity (N\u2009=\u2009135,430), iron (N\u2009=\u2009163,511) and transferrin saturation (N\u2009=\u2009131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.", + "abstract": "

Objective

To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic.

Design

Population based cohort study, on behalf of NHS England.

Setting

Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020).

Participants

Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020.

Main outcome measures

Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household.

Results

Among 9\u2009334\u2009392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or intensive care admission, or death from covid-19. In wave 2, among adults aged 65 years and under, living with children of any age was associated with an increased risk of recorded SARS-CoV-2 infection (hazard ratio 1.06 (95% confidence interval 1.05 to 1.08) for living with children aged 0-11 years; 1.22 (1.20 to 1.24) for living with children aged 12-18 years) and covid-19 related hospital admission (1.18 (1.06 to 1.31) for living with children aged 0-11; 1.26 (1.12 to 1.40) for living with children aged 12-18). Living with children aged 0-11 was associated with reduced risk of death from both covid-19 and non-covid-19 causes in both waves; living with children of any age was also associated with lower risk of dying from non-covid-19 causes. For adults 65 years and under during wave 2, living with children aged 0-11 years was associated with an increased absolute risk of having SARS-CoV-2 infection recorded of 40-60 per 10\u2009000 people, from 810 to between 850 and 870, and an increase in the number of hospital admissions of 1-5 per 10\u2009000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10\u2009000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10\u2009000 in the number of hospital admissions.

Conclusions

In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.", "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s42003-020-01575-z; html:https://europepmc.org/articles/PMC7859200; pdf:https://europepmc.org/articles/PMC7859200?pdf=render" + "urls": "doi:https://doi.org/10.1136/bmj.n628; html:https://europepmc.org/articles/PMC7970340; pdf:https://europepmc.org/articles/PMC7970340?pdf=render; pdf:https://www.bmj.com/content/bmj/372/bmj.n628.full.pdf" }, { - "id": "33737413", - "doi": "https://doi.org/10.1136/bmj.n628", - "title": "Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England.", - "authorString": "Forbes H, Morton CE, Bacon S, McDonald HI, Minassian C, Brown JP, Rentsch CT, Mathur R, Schultze A, DeVito NJ, MacKenna B, Hulme WJ, Croker R, Walker AJ, Williamson EJ, Bates C, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Drysdale H, Wong AYS, Cockburn J, McManus R, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Evans SJW, Bhaskaran K, Eggo RM, Goldacre B, Tomlinson LA.", + "id": "33536631", + "doi": "https://doi.org/10.1038/s42003-020-01575-z", + "title": "A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.", + "authorString": "Bell S, Rigas AS, Magnusson MK, Ferkingstad E, Allara E, Bjornsdottir G, Ramond A, S\u00f8rensen E, Halldorsson GH, Paul DS, Burgdorf KS, Eggertsson HP, Howson JMM, Th\u00f8rner LW, Kristmundsdottir S, Astle WJ, Erikstrup C, Sigurdsson JK, Vuckovic D, Dinh KM, Tragante V, Surendran P, Pedersen OB, Vidarsson B, Jiang T, Paarup HM, Onundarson PT, Akbari P, Nielsen KR, Lund SH, Juliusson K, Magnusson MI, Frigge ML, Oddsson A, Olafsson I, Kaptoge S, Hjalgrim H, Runarsson G, Wood AM, Jonsdottir I, Hansen TF, Sigurdardottir O, Stefansson H, Rye D, DBDS Genomic Consortium, Peters JE, Westergaard D, Holm H, Soranzo N, Banasik K, Thorleifsson G, Ouwehand WH, Thorsteinsdottir U, Roberts DJ, Sulem P, Butterworth AS, Gudbjartsson DF, Danesh J, Brunak S, Di Angelantonio E, Ullum H, Stefansson K.", "authorAffiliations": "", - "journalTitle": "BMJ (Clinical research ed.)", + "journalTitle": "Communications biology", "pubYear": "2021", - "date": "2021-03-18", + "date": "2021-02-03", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic.

Design

Population based cohort study, on behalf of NHS England.

Setting

Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020).

Participants

Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020.

Main outcome measures

Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household.

Results

Among 9\u2009334\u2009392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or intensive care admission, or death from covid-19. In wave 2, among adults aged 65 years and under, living with children of any age was associated with an increased risk of recorded SARS-CoV-2 infection (hazard ratio 1.06 (95% confidence interval 1.05 to 1.08) for living with children aged 0-11 years; 1.22 (1.20 to 1.24) for living with children aged 12-18 years) and covid-19 related hospital admission (1.18 (1.06 to 1.31) for living with children aged 0-11; 1.26 (1.12 to 1.40) for living with children aged 12-18). Living with children aged 0-11 was associated with reduced risk of death from both covid-19 and non-covid-19 causes in both waves; living with children of any age was also associated with lower risk of dying from non-covid-19 causes. For adults 65 years and under during wave 2, living with children aged 0-11 years was associated with an increased absolute risk of having SARS-CoV-2 infection recorded of 40-60 per 10\u2009000 people, from 810 to between 850 and 870, and an increase in the number of hospital admissions of 1-5 per 10\u2009000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10\u2009000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10\u2009000 in the number of hospital admissions.

Conclusions

In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.", + "abstract": "Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N\u2009=\u2009246,139), total iron binding capacity (N\u2009=\u2009135,430), iron (N\u2009=\u2009163,511) and transferrin saturation (N\u2009=\u2009131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.", "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmj.n628; html:https://europepmc.org/articles/PMC7970340; pdf:https://europepmc.org/articles/PMC7970340?pdf=render; pdf:https://www.bmj.com/content/bmj/372/bmj.n628.full.pdf" + "urls": "doi:https://doi.org/10.1038/s42003-020-01575-z; html:https://europepmc.org/articles/PMC7859200; pdf:https://europepmc.org/articles/PMC7859200?pdf=render" }, { "id": "30814958", @@ -37688,23 +37722,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41588-020-00762-2; html:https://europepmc.org/articles/PMC7611259; pdf:https://europepmc.org/articles/PMC7611259?pdf=render; pdf:https://europepmc.org/articles/pmc7611259?pdf=render" }, - { - "id": "35013731", - "doi": "https://doi.org/10.1016/j.lanepe.2021.100299", - "title": "Persistent hesitancy for SARS-CoV-2 vaccines among healthcare workers in the United Kingdom: analysis of longitudinal data from the UK-REACH cohort study.", - "authorString": "Martin CA, Woolf K, Bryant L, Carr S, Gray LJ, Gupta A, Guyatt AL, John C, Melbourne C, McManus IC, Nazareth J, Nellums LB, Tobin MD, Pan D, Khunti K, Pareek M, UK-REACH Study Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "The Lancet regional health. Europe", - "pubYear": "2022", - "date": "2022-01-04", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.lanepe.2021.100299; html:https://europepmc.org/articles/PMC8730737; pdf:https://europepmc.org/articles/PMC8730737?pdf=render" - }, { "id": "34773122", "doi": "https://doi.org/10.1038/s41588-021-00977-x", @@ -37722,6 +37739,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41588-021-00977-x" }, + { + "id": "35013731", + "doi": "https://doi.org/10.1016/j.lanepe.2021.100299", + "title": "Persistent hesitancy for SARS-CoV-2 vaccines among healthcare workers in the United Kingdom: analysis of longitudinal data from the UK-REACH cohort study.", + "authorString": "Martin CA, Woolf K, Bryant L, Carr S, Gray LJ, Gupta A, Guyatt AL, John C, Melbourne C, McManus IC, Nazareth J, Nellums LB, Tobin MD, Pan D, Khunti K, Pareek M, UK-REACH Study Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "The Lancet regional health. Europe", + "pubYear": "2022", + "date": "2022-01-04", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.lanepe.2021.100299; html:https://europepmc.org/articles/PMC8730737; pdf:https://europepmc.org/articles/PMC8730737?pdf=render" + }, { "id": "32573913", "doi": "https://doi.org/10.1002/alz.12106",